CEBPA encodes C/EBPalpha, a basic leucine-zipper transcription factor that recognizes cis-regulatory DNA as a homodimer or heterodimer and coordinates differentiation with proliferative restraint. Its N-terminal regulatory regions and interacting transcription factors shape promoter-specific activation and repression. C/EBPalpha drives granulocytic and adipocyte gene programs and contributes to differentiated functions in liver and lung. The p42 and N-terminally truncated p30 products share the C-terminal DNA-binding and dimerization region but differ in regulatory potency; an N-terminally extended product is associated with nucleolar rDNA regulation. C/EBPalpha also associates with cell-cycle regulatory proteins, linking transcriptional control to cell-cycle arrest in a product- and phosphorylation-dependent manner. Disruptive CEBPA variants impair myeloid differentiation and predispose to acute myeloid leukemia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA can repress transcription in a promoter- and partner-dependent context. Reason: C/EBPalpha is not exclusively an activator. The original PMID:23814099 abstract reports CEBPA occupancy and repression of the IL10 promoter, relieved by an IL32beta/PKCdelta-dependent change. Independent PMID:11672531 documents E2F repression and its requirement for differentiation in mouse genetic models. These support conserved contextual repression without making every CEBPA product or promoter repressive. The original electronic or similarity source remains unchanged. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | KEEP AS NON CORE | Summary: CEBPA associates with regulatory chromatin. Reason: The TFClass classification is corroborated by endogenous human CEBPA ChIP at EVI2B and CCL2 regulatory regions in PMID:28186500 and PMID:24429361. This supports chromatin association, not constitutive incorporation into a nucleosome. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:12695546 Transcriptional regulation of human CYP3A4 basal expression ... | MODIFY | Summary: CEBPA binds cis-regulatory DNA at RNA polymerase II target genes. Reason: The broader cis-regulatory binding term can be made polymerase-specific. Human CYP3A4 promoter binding, mutational reporter analysis and endogenous expression are reported in PMID:12695546; human EVI2B ChIP and promoter-mutant assays in Figure 2 of PMID:28186500 independently establish regulatory-site recognition. Preserve the original experimental or ortholog source and use RNA polymerase II cis-regulatory region sequence-specific DNA binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:28186500 EVI2B is a C/EBPΞ± target gene required for granulocytic diff... | MODIFY | Summary: CEBPA binds cis-regulatory DNA at RNA polymerase II target genes. Reason: The broader cis-regulatory binding term can be made polymerase-specific. Human CYP3A4 promoter binding, mutational reporter analysis and endogenous expression are reported in PMID:12695546; human EVI2B ChIP and promoter-mutant assays in Figure 2 of PMID:28186500 independently establish regulatory-site recognition. Preserve the original experimental or ortholog source and use RNA polymerase II cis-regulatory region sequence-specific DNA binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | MODIFY | Summary: CEBPA binds cis-regulatory DNA at RNA polymerase II target genes. Reason: The broader cis-regulatory binding term can be made polymerase-specific. Human CYP3A4 promoter binding, mutational reporter analysis and endogenous expression are reported in PMID:12695546; human EVI2B ChIP and promoter-mutant assays in Figure 2 of PMID:28186500 independently establish regulatory-site recognition. Preserve the original experimental or ortholog source and use RNA polymerase II cis-regulatory region sequence-specific DNA binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: CEBPA has an inherited sequence-specific regulatory DNA-binding activity. Reason: Retain PAINT node PTN001515662, independently corroborated by human promoter binding and reporter experiments. The node represents a curator-assessed ancestral function, not a vote among donor proteins. The full ancestral reconstruction was not repeated, and no target-specific loss contradicts this CEBP-family activity. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: CEBPA recognizes RNA polymerase II regulatory DNA. Reason: The rodent ortholog transfer is consistent with human CEBPA binding to defined CSF3R, CYP3A4 and EVI2B regulatory sequences. This is an intrinsic bZIP DNA-recognition function; the original rodent source objects are retained. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: CEBPA is a conserved RNA polymerase II DNA-binding transcription factor. Reason: Retain the PAINT assertion at PTN001515662. Human WT CEBPA DNA-binding and transactivation experiments in PMID:11242107 and endogenous target occupancy in PMID:28186500 corroborate the family-level inference. Product-specific differences in potency do not negate the gene-level function, and the ancestral node placement has not been re-inferred here. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA is a sequence-specific regulator of RNA polymerase II transcription. Reason: The ortholog or TFClass assertion agrees with human promoter binding and functional target-gene assays. The bZIP region recognizes regulatory DNA, while N-terminal regulatory regions and interacting factors determine the output; neither annotation implies that all alternative products have equal transactivation potency. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: CEBPA is a sequence-specific regulator of RNA polymerase II transcription. Reason: The ortholog or TFClass assertion agrees with human promoter binding and functional target-gene assays. The bZIP region recognizes regulatory DNA, while N-terminal regulatory regions and interacting factors determine the output; neither annotation implies that all alternative products have equal transactivation potency. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: CEBPA activates transcription at differentiation-associated target genes. Reason: The rodent similarity inference is independently corroborated by human WT CEBPA activation of CSF3R and CYP3A4 reporters and endogenous target expression. Activation is a central activity despite separate repressive contexts and the weaker N-terminally truncated p30 product. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IMP PMID:16946298 STAT3 mediates hepatic hepcidin expression and its inflammat... | ACCEPT | Summary: CEBPA supports basal HAMP transcription in human liver cells. Reason: The original full primary Results and Figure 3 of PMID:16946298 explicitly test CEBPA: deleting a promoter region containing its site reduces reporter output, and CEBPA siRNA reduces endogenous HAMP RNA in Huh7 cells. The STAT3-focused title does not exclude these CEBPA experiments. This corroborates its established transcription-activator function. Supporting Evidence: |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA activates transcription at differentiation-associated target genes. Reason: The rodent similarity inference is independently corroborated by human WT CEBPA activation of CSF3R and CYP3A4 reporters and endogenous target expression. Activation is a central activity despite separate repressive contexts and the weaker N-terminally truncated p30 product. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS PMID:36228616 Obesity caused by an OVOL2 mutation reveals dual roles of OV... | ACCEPT | Summary: The mouse OVOL2 experiments support CEBPA-dependent transcriptional activation. Reason: Selected full PMID:36228616 Results Figure 6 show CEBPA reporter activity, DNA binding and occupancy at adipogenic target promoters, inhibited by OVOL2. Retain the explicit mouse-to-human similarity assertion; cultured human OVOL2 experiments do not convert every mouse CEBPA assay into a direct human-protein experiment. Supporting Evidence: |
| GO:0001889 liver development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA regulates hepatocyte differentiation during liver development. Reason: Mouse Cebpa loss and hepatoblast transplantation in the original abstract of PMID:17021047 support a lineage-regulatory role, with altered Hnf6/Hnf1b expression and biliary versus hepatic differentiation. Retain the conserved organ-development role as contextual rather than a separate molecular activity; do not reduce the evidence to expression alone. Supporting Evidence: |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Sequence-specific cis-regulatory binding better describes CEBPA than generic DNA binding. Reason: The bZIP transcription factor binds defined regulatory elements. PMID:11242107 directly assays a human CSF3R probe and transcriptional output; PMID:8643605 reports CEBPA-dependent activation of the human leptin promoter and loss of induction after mutation of its site. Refine to RNA polymerase II cis-regulatory region sequence-specific DNA binding, without claiming that the broad original term was false. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0003677 DNA binding | TAS PMID:8643605 The adipocyte specific transcription factor C/EBPalpha modul... | MODIFY | Summary: Sequence-specific cis-regulatory binding better describes CEBPA than generic DNA binding. Reason: The bZIP transcription factor binds defined regulatory elements. PMID:11242107 directly assays a human CSF3R probe and transcriptional output; PMID:8643605 reports CEBPA-dependent activation of the human leptin promoter and loss of induction after mutation of its site. Refine to RNA polymerase II cis-regulatory region sequence-specific DNA binding, without claiming that the broad original term was false. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA binds regulatory DNA in chromatin. Reason: Human endogenous ChIP at EVI2B and CCL2 regulatory regions corroborates the conserved chromatin-binding assertion. Retain the broader molecular description as non-core because sequence-specific transcription-factor activity expresses the principal function more precisely; chromatin occupancy alone is not chromatin-remodeling catalysis. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11242107 Dominant-negative mutations of CEBPA, encoding CCAAT/enhance... | MODIFY | Summary: Human WT CEBPA directly activates a granulocyte target promoter. Reason: The original full PMID:11242107 Methods and Figures 3β5 use human WT and mutant CEBPA in DNA-binding and reporter assays. WT binds the CSF3R regulatory probe and activates its reporter. The p30 comparison is probe- and assay-specific, not absence of all p30 DNA binding. Refine this broad TF activity to the demonstrated Pol II activator activity. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11242107 The mutant proteins block wild-type C/EBPalpha DNA binding and transactivation |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:12695546 Transcriptional regulation of human CYP3A4 basal expression ... | MODIFY | Summary: CEBPA activates CYP3A4 through defined regulatory sites. Reason: The original PMID:12695546 abstract explicitly reports mobility-shift, site-mutagenesis and reporter experiments, plus endogenous CYP3A4 induction. These directly support the activator refinement. The cache is abstract-only; detailed construct species and every full-text control were not independently inspected. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:12695546 one proximal and two distal C/EBP alpha binding sites are essential sites |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:15664994 Signal transducers and activators of transcription 3 augment... | MODIFY | Summary: CEBPA transcriptional activation cooperates with activated STAT3. Reason: PMID:15664994 reports increased CEBPA transcriptional output through STAT3 association and conditional CEBPA restoration in G-CSF-treated 32Dcl3 cells. Refine the broad activity to Pol II activator activity while keeping the murine cell context explicit; the abstract does not independently resolve every expression construct. Human activity is separately established in PMID:11242107. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: CEBPA is a RNA polymerase II DNA-binding transcription factor. Reason: The broad TF assignment is biologically correct and can be refined using human promoter-binding and activation experiments. The old mapping/cloning references PMID:1535333 and PMID:9191024 provide gene identity and expression context; they are not presented as if they independently measured all modern target assays. The activity is independently grounded by PMID:11242107 and PMID:12695546. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:1535333 Chromosomal localization in man and rat of the genes encodin... | MODIFY | Summary: CEBPA is a RNA polymerase II DNA-binding transcription factor. Reason: The broad TF assignment is biologically correct and can be refined using human promoter-binding and activation experiments. The old mapping/cloning references PMID:1535333 and PMID:9191024 provide gene identity and expression context; they are not presented as if they independently measured all modern target assays. The activity is independently grounded by PMID:11242107 and PMID:12695546. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:9191024 Transcription factor C/EBPalpha: novel sites of expression a... | MODIFY | Summary: CEBPA is a RNA polymerase II DNA-binding transcription factor. Reason: The broad TF assignment is biologically correct and can be refined using human promoter-binding and activation experiments. The old mapping/cloning references PMID:1535333 and PMID:9191024 provide gene identity and expression context; they are not presented as if they independently measured all modern target assays. The activity is independently grounded by PMID:11242107 and PMID:12695546. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0005515 protein binding | IPI PMID:12692227 The Papillomavirus E2 protein binds to and synergizes with C... | KEEP AS NON CORE | Summary: CEBPA associates with the annotated papillomavirus E2 protein. Reason: The original PMID:12692227 abstract explicitly reports CEBPA/CEBPB co-precipitation with E2 proteins from multiple papillomavirus types and transcriptional cooperation. Retain the exact original viral partner accession and supported low-resolution association. The detailed CEBPA construct and accession-to-panel mapping were not independently recovered; this does not justify denial of the curated interaction or transfer of viral E2 functions to CEBPA. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12692227 The Papillomavirus E2 protein binds to and synergizes with C... | KEEP AS NON CORE | Summary: CEBPA associates with the annotated papillomavirus E2 protein. Reason: The original PMID:12692227 abstract explicitly reports CEBPA/CEBPB co-precipitation with E2 proteins from multiple papillomavirus types and transcriptional cooperation. Retain the exact original viral partner accession and supported low-resolution association. The detailed CEBPA construct and accession-to-panel mapping were not independently recovered; this does not justify denial of the curated interaction or transfer of viral E2 functions to CEBPA. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | KEEP AS NON CORE | Summary: CEBPA associates with RB-containing regulatory complexes. Reason: PMID:15107404 reports CEBPA association with E2FβRB complexes in its phosphorylation and proliferation experiments. Its mechanistic mutagenesis uses mouse CEBPA, with distinct human liver analyses. Retain the observed complex-associated binding and original human partner source; do not claim an isolated direct RB interface or assign RB activity to CEBPA. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | KEEP AS NON CORE | Summary: Human liver CEBPA associates with the BRM chromatin-remodeling factor. Reason: The original PMID:15107404 selected full Results and Figure 8 report endogenous CEBPAβBRM association in control human liver, with altered interactions in tumors. Retain the SMARCA2/P51531 association at co-immunoprecipitation resolution. The separate mouse phosphosite experiments do not establish a human residue-specific mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16490787 In prostate cancer cells the interaction of C/EBPalpha with ... | KEEP AS NON CORE | Summary: CEBPA associates with PARP1 in prostate cancer cells. Reason: Exact human target-linked IntAct records EBI-1253144 and EBI-1253393 match PMID:16490787 and PARP1/P09874, with co-immunoprecipitation in prostate cancer cells. The original abstract additionally describes purified-protein pull-downs, but the curated records are not themselves proof of every direct-interface assay. Retain the association without assigning PARP1 catalytic activity to CEBPA. |
| GO:0005515 protein binding | IPI PMID:19059241 Homeodomain transcription factor CDX1 is required for the tr... | MODIFY | Summary: CEBPA binds the DNA-binding transcription factor CDX1. Reason: The original PMID:19059241 abstract reports a CDX1βCEBPA physical interaction that increases with butyrate and supports PPARgamma transcription. CDX1 is the homeobox DNA-binding transcription-factor partner; GO:0140297 is more informative than generic binding. Full construct and interface details remain outside the accessed abstract. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20075868 Nucleolar retention of a translational C/EBPalpha isoform st... | KEEP AS NON CORE | Summary: CEBPA associates with UBTF/UBF1 in a nucleolar regulatory context. Reason: Full PMID:20075868 co-immunoprecipitation uses rat CEBPA products expressed in human cells; both p42 and the extended product associate with UBF1. Retain the original association, without claiming an extended-product-exclusive interaction, a purified interface, or intrinsic Pol I catalysis. Human endogenous localization and translation experiments provide separate corroboration of product context. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with CEBPB in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and CEBPB leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with ATF4 in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and ATF4 leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with DDIT3 in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and DDIT3 leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with CEBPD in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and CEBPD leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with CEBPG in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and CEBPG leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with BATF in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and BATF leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. The signal is weaker and asymmetric between array orientations; it is not characterized as uniformly strong. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with ATF5 in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and ATF5 leucine-zipper peptides. The target cells and heatmap support heterodimerization, which is more informative than the original binding term. The signal is weaker and asymmetric between array orientations; it is not characterized as uniformly strong. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with FOS in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβFOS domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with ATF3 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβATF3 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-6469, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with ATF4 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβATF4 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-6525, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with DDIT3 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβDDIT3 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with CEBPG in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβCEBPG domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with CEBPE in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβCEBPE domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with BATF in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβBATF domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-7006, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with BATF2 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβBATF2 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-7065, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with BATF3 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβBATF3 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-7095, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show dimerization with ATF5 in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβATF5 domain pair. Those primary measurements support heterodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-6586, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:23814099 Interleukin (IL)-32Ξ²-mediated CCAAT/enhancer-binding protein... | KEEP AS NON CORE | Summary: CEBPA associates with the exact IL32beta isoform P24001-2. Reason: Positive human IntAct records for PMID:23814099 preserve the beta isoform, tagged full-length and fragment contexts, and HEK293/U937 co-immunoprecipitation. EBI-9975676 records the CEBPA 250β358 sufficient binding region; other records include the IL32beta 1β67 fragment. Retain the association without changing the original isoform or inferring cytokine-receptor activity by CEBPA. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The BioPlex screen supports a CEBPAβDDIT3 association. Reason: The exact human PMID:33961781 record EBI-54644668 uses tagged DDIT3 bait in HEK293T cells and CEBPA as prey. Retain this affinity-purification association as non-core. Independent bZIP assays support a heterodimer elsewhere, but this screen itself does not resolve a binary interface or establish a stress-response program. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | KEEP AS NON CORE | Summary: HaloMS supports the CEBPAβPARP1 association. Reason: Exact source-linked human records EBI-67179659 and EBI-67186949 match PMID:38884001 and the original partner. The full primary Methods/Results describe immobilized, in-vitro-expressed HaloTag query proteins exposed to cell lysates. Retain this association at complex-capture resolution, without calling it an endogenous binary interaction or assigning the partner's molecular activity to CEBPA. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | KEEP AS NON CORE | Summary: HaloMS supports the CEBPAβUBTF association. Reason: Exact source-linked human records EBI-67184047 match PMID:38884001 and the original partner. The full primary Methods/Results describe immobilized, in-vitro-expressed HaloTag query proteins exposed to cell lysates. Retain this association at complex-capture resolution, without calling it an endogenous binary interaction or assigning the partner's molecular activity to CEBPA. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | KEEP AS NON CORE | Summary: HaloMS supports the CEBPAβCEBPB association. Reason: Exact source-linked human records EBI-67179659 and EBI-67186949 match PMID:38884001 and the original partner. The full primary Methods/Results describe immobilized, in-vitro-expressed HaloTag query proteins exposed to cell lysates. Retain this association at complex-capture resolution, without calling it an endogenous binary interaction or assigning the partner's molecular activity to CEBPA. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | KEEP AS NON CORE | Summary: HaloMS supports the CEBPAβATF3 association. Reason: Exact source-linked human records EBI-67179261 match PMID:38884001 and the original partner. The full primary Methods/Results describe immobilized, in-vitro-expressed HaloTag query proteins exposed to cell lysates. Retain this association at complex-capture resolution, without calling it an endogenous binary interaction or assigning the partner's molecular activity to CEBPA. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: CEBPA performs its transcriptional function in the nucleus. Reason: Retain the PAINT nuclear active-in assertion at PTN001515662. Human nuclear localization and sequence-specific transcriptional assays independently corroborate nuclear function. The ancestral reconstruction was not repeated; self or few descendant evidences are not a reason to reject PAINT. |
| GO:0005634 nucleus | IDA PMID:11242107 Dominant-negative mutations of CEBPA, encoding CCAAT/enhance... | ACCEPT | Summary: Human WT and tested p30 CEBPA localize to the nucleus. Reason: Original PMID:11242107 Figure 4 immunolocalizes human WT and mutant CEBPA expressed in CV1 cells. This directly supports the nuclear location while preserving the source annotation without adding a product tag. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005634 nucleus | ISS PMID:36228616 Obesity caused by an OVOL2 mutation reveals dual roles of OV... | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005634 nucleus | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005634 nucleus | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005634 nucleus | NAS PMID:8657121 Stress-induced binding of the transcriptional factor CHOP to... | ACCEPT | Summary: CEBPA is a nuclear transcription factor. Reason: Retain the electronic, similarity or complex-context location, independently supported by human CEBPA immunolocalization in PMID:11242107 and nuclear target occupancy and complex assays in PMID:24429361. The bZIP-domain screens and the mouse OVOL2 assays are not represented as independent localization measurements of every human product. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: CEBPA is detected in the nucleoplasm. Reason: Retain the atlas localization as consistent with human nuclear transcriptional function. The original GO_REF:0000052 imaging assertion is not used to infer a nucleoplasmic catalytic activity or to exclude the separate extended-product nucleolar pool. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9617207 | KEEP AS NON CORE | Summary: The curated nuclear reaction context is consistent with CEBPA localization. Reason: The original Reactome reaction places CEBPA in the nucleoplasm during a regulatory interaction. Human nuclear localization and promoter occupancy independently corroborate this compartment. Retain that location without treating every enclosing Reactome pathway as a process performed by CEBPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9622363 | KEEP AS NON CORE | Summary: The recovered human KLF5 promoter-binding event supports the curated nuclear context. Reason: A later retrieval recovered the exact Reactome event: human CEBPA binds sites upstream of the KLF5 transcription start site. Retain the original curated nucleoplasm location, consistent with independent human nuclear localization and promoter occupancy. The brief event cache verifies the target/source identity; it is not presented as a new microscopic compartment assay or as evidence that CEBPA performs every enclosing pathway. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9624112 | KEEP AS NON CORE | Summary: The curated nuclear reaction context is consistent with CEBPA localization. Reason: The original Reactome reaction places CEBPA in the nucleoplasm during a regulatory interaction. Human nuclear localization and promoter occupancy independently corroborate this compartment. Retain that location without treating every enclosing Reactome pathway as a process performed by CEBPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9624120 | KEEP AS NON CORE | Summary: The curated nuclear reaction context is consistent with CEBPA localization. Reason: The original Reactome reaction places CEBPA in the nucleoplasm during a regulatory interaction. Human nuclear localization and promoter occupancy independently corroborate this compartment. Retain that location without treating every enclosing Reactome pathway as a process performed by CEBPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9624668 | KEEP AS NON CORE | Summary: The curated nuclear reaction context is consistent with CEBPA localization. Reason: The original Reactome reaction places CEBPA in the nucleoplasm during a regulatory interaction. Human nuclear localization and promoter occupancy independently corroborate this compartment. Retain that location without treating every enclosing Reactome pathway as a process performed by CEBPA. |
| GO:0005667 transcription regulator complex | IDA PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | MODIFY | Summary: CEBPA forms a RNA polymerase II transcription-regulatory complex. Reason: Selected full PMID:24429361 Results and Figure 4 show endogenous CEBPA co-immunoprecipitating PU.1 and STAT3 in IL6-treated human hepatocytes, with CCL2-promoter ChIP and functional reporter cooperation. The demonstrated target is transcribed by Pol II, supporting the more specific complex term. Co-IP is not an isolated pairwise-interface measurement. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | MODIFY | Summary: CEBPA participates in Pol II transcription-regulatory complexes. Reason: The broad mouse-based complex assertion is corroborated by human CCL2-promoter regulatory complexes in PMID:24429361 and CEBPA bZIP dimerization. Refine to the Pol II complex while preserving the ortholog source; the separate extended-product Pol I activity is not used to define these promoter complexes. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A CEBPA product can occupy the nucleolus. Reason: Full PMID:20075868 links the N-terminally extended product to nucleolar enrichment, UBF1-associated rDNA regulation and increased rRNA output. Engineered localization and function experiments predominantly use rat constructs in human cells; human endogenous and initiation-site data supply distinct corroboration. Retain gene-level nucleolar localization without extending it uniformly to p42, p30 or the displayed product. Supporting Evidence: PMID:20075868 a basic amino-acid motif within its N-terminus is required for nucleolar retention |
| GO:0006091 generation of precursor metabolites and energy | TAS PMID:8643605 The adipocyte specific transcription factor C/EBPalpha modul... | MODIFY | Summary: The leptin-promoter study supports transcriptional regulation rather than energy-generating chemistry. Reason: GO:0006091 concerns chemical reactions forming precursor metabolites or releasing energy. PMID:8643605 directly reports CEBPA-dependent induction of a human leptin promoter and loss of induction after mutation of its CEBPA site. Refine this TAS assertion to positive regulation of transcription by RNA polymerase II, the work performed by the factor. The physiological energy-balance role of leptin is not assigned as energy-generating chemistry by CEBPA. This refinement identifies the directly documented promoter-regulatory process; incomplete full-body access is not evidence excluding all metabolic participation. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: CEBPA regulates transcription rather than supplying the polymerase reaction. Reason: The InterPro-derived broad transcription term can be stated more precisely as regulation of transcription by RNA polymerase II. Sequence-specific promoter binding, reporter changes and endogenous target regulation establish the regulatory step; CEBPA is not the RNA polymerase. Proposed replacements: regulation of transcription by RNA polymerase II |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:15664994 Signal transducers and activators of transcription 3 augment... | MODIFY | Summary: CEBPA regulates Pol II target expression downstream of G-CSF signaling. Reason: PMID:15664994 reports STAT3-associated augmentation of CEBPA transcriptional activity and target-gene output in G-CSF-treated murine 32Dcl3 cells. Refine the generic transcription-regulation term to the Pol II process while preserving the original IDA provenance and construct-access limitation. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: CEBPA regulates RNA polymerase II target genes. Reason: The broad keyword-derived transcription-regulation term is sound but less informative than the Pol II regulatory function established by promoter-binding and transcriptional assays. No RNA-polymerase catalytic activity is assigned to CEBPA. Proposed replacements: regulation of transcription by RNA polymerase II |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: CEBPA has an inherited role in Pol II transcriptional regulation. Reason: Retain PAINT node PTN001515662: human CEBPA promoter binding and functional target assays corroborate its conserved regulatory role. Both activation and context-dependent repression fit this broad process. The ancestral node was not reconstructed or rejected based on donor count. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | KEEP AS NON CORE | Summary: CEBPA dimerization supports its transcription-regulatory role. Reason: These complex-context NAS assertions accompany purified bZIP interaction studies. Dimerization alone does not measure a transcriptional program, but human promoter-binding and activation experiments independently establish Pol II regulation. Retain that correct broad role while keeping the interaction-study assay and physiological corroboration distinct. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | KEEP AS NON CORE | Summary: CEBPA dimerization supports its transcription-regulatory role. Reason: These complex-context NAS assertions accompany purified bZIP interaction studies. Dimerization alone does not measure a transcriptional program, but human promoter-binding and activation experiments independently establish Pol II regulation. Retain that correct broad role while keeping the interaction-study assay and physiological corroboration distinct. |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:14660596 The CCAAT enhancer-binding protein alpha (C/EBPalpha) requir... | KEEP AS NON CORE | Summary: CEBPA p42 can inhibit cell proliferation through a SWI/SNF-dependent mechanism. Reason: Selected original PMID:14660596 Methods and Results compare rat p42 and p30 constructs in cell-proliferation assays, including SWI/SNF-defective and reconstituted contexts. Retain the antiproliferative effect with explicit product and ortholog scope; loss of N-terminal regulatory regions changes the effect. Cell-count assays are not measurements of cell size. Supporting Evidence: PMID:14660596 Reconstitution of SWI/SNF function restores C/EBPalpha-dependent proliferation arrest. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CEBPA can restrain proliferation as part of terminal differentiation. Reason: The conserved antiproliferative role is supported by mouse genetic E2F-repression mutants and p42/SWI-SNF-dependent proliferation experiments. It is product- and context-dependent, and is not assumed for all p30 or transformed-cell settings. Retain the original electronic/similarity assertions without conflating proliferation with cell size. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA can restrain proliferation as part of terminal differentiation. Reason: The conserved antiproliferative role is supported by mouse genetic E2F-repression mutants and p42/SWI-SNF-dependent proliferation experiments. It is product- and context-dependent, and is not assumed for all p30 or transformed-cell settings. Retain the original electronic/similarity assertions without conflating proliferation with cell size. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA can restrain proliferation as part of terminal differentiation. Reason: The conserved antiproliferative role is supported by mouse genetic E2F-repression mutants and p42/SWI-SNF-dependent proliferation experiments. It is product- and context-dependent, and is not assumed for all p30 or transformed-cell settings. Retain the original electronic/similarity assertions without conflating proliferation with cell size. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: CEBPA positively regulates gene expression at the transcriptional level. Reason: Human promoter-binding and activation experiments locate the performed step at RNA polymerase II transcription. Refine the broad positive-expression transfer accordingly, rather than implying a demonstrated translational or protein-stability activity for every target. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0019221 cytokine-mediated signaling pathway | NAS PMID:15664994 Signal transducers and activators of transcription 3 augment... | KEEP AS NON CORE | Summary: CEBPA is a transcriptional effector in cytokine signaling. Reason: The original PMID:15664994 abstract directly couples activated STAT3 to CEBPA-dependent target expression and granulocytic differentiation after G-CSF stimulation in 32Dcl3 cells. This is functional signal-to-transcription coupling, not merely induced CEBPA expression; retain the broad cytokine pathway as contextual. Supporting Evidence: |
| GO:0019900 kinase binding | IEA GO_REF:0000107 | MODIFY | Summary: CEBPA associates with cyclin-dependent protein kinases. Reason: Selected full PMID:15107404 Results and Figure 8 show endogenous CEBPA association with CDK2 and CDK4 in control human liver. Its phosphorylation-site mechanistic experiments use mouse CEBPA. Refine kinase binding to protein kinase binding, preserving each original partner. Do not convert the original IPI binding event into a purified-human inhibition assay. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0019900 kinase binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | MODIFY | Summary: CEBPA associates with cyclin-dependent protein kinases. Reason: Selected full PMID:15107404 Results and Figure 8 show endogenous CEBPA association with CDK2 and CDK4 in control human liver. Its phosphorylation-site mechanistic experiments use mouse CEBPA. Refine kinase binding to protein kinase binding, preserving each original partner. Do not convert the original IPI binding event into a purified-human inhibition assay. Proposed replacements: protein kinase binding Supporting Evidence: PMID:15107404 a short region of C/EBPΞ± interacts with cdks |
| GO:0019900 kinase binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | MODIFY | Summary: CEBPA associates with cyclin-dependent protein kinases. Reason: Selected full PMID:15107404 Results and Figure 8 show endogenous CEBPA association with CDK2 and CDK4 in control human liver. Its phosphorylation-site mechanistic experiments use mouse CEBPA. Refine kinase binding to protein kinase binding, preserving each original partner. Do not convert the original IPI binding event into a purified-human inhibition assay. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0030099 myeloid cell differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: CEBPA performs a conserved myeloid differentiation program. Reason: Retain PAINT node PTN002762817. Human WT/mutant CEBPA promoter and differentiation studies and direct EVI2B target regulation corroborate the lineage-instructive transcriptional role. The node is not a pairwise transfer and was not challenged on donor count. |
| GO:0030099 myeloid cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA drives myeloid differentiation through target-gene regulation. Reason: Human CEBPA target-binding and disease-mutation experiments independently establish this core role. The G-CSF/STAT3 study uses a murine 32Dcl3 cellular context, which is retained as ortholog corroboration rather than silently relabeled as human direct evidence. |
| GO:0030099 myeloid cell differentiation | NAS PMID:15664994 Signal transducers and activators of transcription 3 augment... | ACCEPT | Summary: CEBPA drives myeloid differentiation through target-gene regulation. Reason: Human CEBPA target-binding and disease-mutation experiments independently establish this core role. The G-CSF/STAT3 study uses a murine 32Dcl3 cellular context, which is retained as ortholog corroboration rather than silently relabeled as human direct evidence. |
| GO:0030324 lung development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA regulates maturation of the lung epithelium. Reason: The original donor literature includes conditional mouse respiratory-epithelial Cebpa deletion with impaired surfactant-gene expression, maturation and neonatal function (PMID:16467360). Retain the organ-development transfer as a tissue-specific transcriptional role, with mouse experimental scope explicit. |
| GO:0030851 granulocyte differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA is a lineage-instructive regulator of granulocyte differentiation. Reason: Human WT and AML-associated mutant CEBPA experiments connect target-gene activation with granulocytic differentiation. Mouse E2F-repression-deficient alleles further link differentiation to proliferative restraint. These establish performed transcriptional work rather than an expression-only correlation. |
| GO:0030851 granulocyte differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA is a lineage-instructive regulator of granulocyte differentiation. Reason: Human WT and AML-associated mutant CEBPA experiments connect target-gene activation with granulocytic differentiation. Mouse E2F-repression-deficient alleles further link differentiation to proliferative restraint. These establish performed transcriptional work rather than an expression-only correlation. |
| GO:0031490 chromatin DNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA binds regulatory DNA in chromatin. Reason: Human endogenous ChIP at EVI2B and CCL2 regulatory regions corroborates the conserved chromatin-binding assertion. Retain the broader molecular description as non-core because sequence-specific transcription-factor activity expresses the principal function more precisely; chromatin occupancy alone is not chromatin-remodeling catalysis. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | KEEP AS NON CORE | Summary: CEBPA can promote ubiquitin-dependent CDK4 turnover. Reason: The accessible original PMID:14685163 review explicitly discusses CEBPA-associated CDK degradation and arrest. Independent primary PMID:11867521 reports CDK4 ubiquitin conjugates, turnover and MG132 sensitivity in mouse/cultured-cell systems. Retain the contextual regulatory process, without assigning protease or ubiquitin-ligase catalysis to CEBPA or generalizing CDK4 turnover to CDK2. |
| GO:0036488 CHOP-C/EBP complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA forms a heterodimeric complex with CHOP/DDIT3. Reason: The original human bZIP screen and publisher Table S2 positively support CEBPAβDDIT3 dimerization; CPX-69 records the curated CHOPβCEBPA complex. Retain that specific complex without assuming every associated stress pathway is performed by this exact heterodimer. |
| GO:0036488 CHOP-C/EBP complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | KEEP AS NON CORE | Summary: CEBPA forms a heterodimeric complex with CHOP/DDIT3. Reason: The original human bZIP screen and publisher Table S2 positively support CEBPAβDDIT3 dimerization; CPX-69 records the curated CHOPβCEBPA complex. Retain that specific complex without assuming every associated stress pathway is performed by this exact heterodimer. |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA regulates glucose homeostasis through hepatic transcription. Reason: Mouse Cebpa knockout and domain-selective knock-in experiments link hepatic gluconeogenic target expression to systemic glucose phenotypes. The factor performs transcriptional regulation rather than glucose catalysis. Retain the conserved physiological process with donor-species limits and without making every phenotype a separate core activity. |
| GO:0042593 glucose homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA regulates glucose homeostasis through hepatic transcription. Reason: Mouse Cebpa knockout and domain-selective knock-in experiments link hepatic gluconeogenic target expression to systemic glucose phenotypes. The factor performs transcriptional regulation rather than glucose catalysis. Retain the conserved physiological process with donor-species limits and without making every phenotype a separate core activity. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | MODIFY | Summary: CEBPA self-association is homodimerization. Reason: Purified human CEBPA bZIP-domain interaction measurements and the original 2010 publisher target matrix support a homodimer. Refine identical-protein binding to protein homodimerization activity; this does not establish equal dimer abundance for all alternative products in every cell. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Human CEBPA bZIP domains show self-association in direct interaction measurements. Reason: The original primary Methods and publisher supplement Figure S2/Table S2 directly assay purified human CEBPA and CEBPA leucine-zipper peptides. The target cells and heatmap support homodimerization, which is more informative than the original binding term. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Human CEBPA bZIP domains show self-association in direct interaction measurements. Reason: The original paper assays solution bZIP dimerization. Its released target supplement remains inaccessible, but the first author's 2012 MIT thesis Chapter 5 Methods and Table 5.2 directly report the human CEBPAβCEBPA domain pair. Those primary measurements support homodimerization and are explicitly distinguished from uninspected 2013 table cells. The exact human pair is additionally linked to PMID:23661758 in CPX-71, which is source-linked curation rather than independent replication. This is a purified domain-capacity result, not evidence that all full-length CEBPA products form this partnership in cells or execute a particular transcriptional program. Proposed replacements: protein homodimerization activity |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA homodimerization supplies its DNA-binding transcription-factor architecture. Reason: The conserved bZIP self-association is directly corroborated by purified human leucine-zipper measurements in PMID:20102225 and source-linked 2013/thesis affinity evidence. Retain homodimerization as part of the principal transcription-factor mechanism without claiming constitutive dimer occupancy in every product or tissue. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA homodimerization supplies its DNA-binding transcription-factor architecture. Reason: The conserved bZIP self-association is directly corroborated by purified human leucine-zipper measurements in PMID:20102225 and source-linked 2013/thesis affinity evidence. Retain homodimerization as part of the principal transcription-factor mechanism without claiming constitutive dimer occupancy in every product or tissue. |
| GO:0043032 positive regulation of macrophage activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA supports a macrophage activation program. Reason: The donor PMID:21131957 full Results directly include conditional Cebpa deletion and reduced PU.1 and activation-marker expression in mouse macrophages. This is not inferred solely from miR124 effects. Retain the conserved contextual regulatory role, while keeping the human similarity inference distinct from mouse experiments. Supporting Evidence: |
| GO:0043032 positive regulation of macrophage activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA supports a macrophage activation program. Reason: The donor PMID:21131957 full Results directly include conditional Cebpa deletion and reduced PU.1 and activation-marker expression in mouse macrophages. This is not inferred solely from miR124 effects. Retain the conserved contextual regulatory role, while keeping the human similarity inference distinct from mouse experiments. Supporting Evidence: |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Sequence-specific cis-regulatory binding better describes CEBPA than generic DNA binding. Reason: The bZIP transcription factor binds defined regulatory elements. PMID:11242107 directly assays a human CSF3R probe and transcriptional output; PMID:8643605 reports CEBPA-dependent activation of the human leptin promoter and loss of induction after mutation of its site. Refine to RNA polymerase II cis-regulatory region sequence-specific DNA binding, without claiming that the broad original term was false. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA drives adipocyte differentiation through its transcriptional program. Reason: Mouse genetic E2F-repression mutants and CEBPA promoter-engagement experiments support a lineage-regulatory role in adipogenesis. Human CEBPA DNA-binding and target-gene activation provide conserved molecular grounding. Retain the explicit rodent transfer; adipocyte differentiation is distinct from cell division or cell enlargement. |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA drives adipocyte differentiation through its transcriptional program. Reason: Mouse genetic E2F-repression mutants and CEBPA promoter-engagement experiments support a lineage-regulatory role in adipogenesis. Human CEBPA DNA-binding and target-gene activation provide conserved molecular grounding. Retain the explicit rodent transfer; adipocyte differentiation is distinct from cell division or cell enlargement. |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: CEBPA drives adipocyte differentiation through its transcriptional program. Reason: Mouse genetic E2F-repression mutants and CEBPA promoter-engagement experiments support a lineage-regulatory role in adipogenesis. Human CEBPA DNA-binding and target-gene activation provide conserved molecular grounding. Retain the explicit rodent transfer; adipocyte differentiation is distinct from cell division or cell enlargement. |
| GO:0045786 negative regulation of cell cycle | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA couples differentiation to negative regulation of the cell cycle. Reason: Mouse E2F-repression-deficient CEBPA alleles lose proliferative restraint and differentiation capacity, and human liver CEBPA associates with CDK regulatory complexes. Retain the conserved cell-cycle inhibitory role with the product and phosphorylation context explicit; a transformed cell can evade that role without negating the normal activity. Supporting Evidence: PMID:11672531 E2F repression by C/EBPalpha is critical for its ability to induce terminal differentiation |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CEBPA can repress transcription in a promoter- and partner-dependent context. Reason: C/EBPalpha is not exclusively an activator. The original PMID:23814099 abstract reports CEBPA occupancy and repression of the IL10 promoter, relieved by an IL32beta/PKCdelta-dependent change. Independent PMID:11672531 documents E2F repression and its requirement for differentiation in mouse genetic models. These support conserved contextual repression without making every CEBPA product or promoter repressive. The original electronic or similarity source remains unchanged. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA can repress transcription in a promoter- and partner-dependent context. Reason: C/EBPalpha is not exclusively an activator. The original PMID:23814099 abstract reports CEBPA occupancy and repression of the IL10 promoter, relieved by an IL32beta/PKCdelta-dependent change. Independent PMID:11672531 documents E2F repression and its requirement for differentiation in mouse genetic models. These support conserved contextual repression without making every CEBPA product or promoter repressive. The original electronic or similarity source remains unchanged. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA can repress transcription in a promoter- and partner-dependent context. Reason: C/EBPalpha is not exclusively an activator. The original PMID:23814099 abstract reports CEBPA occupancy and repression of the IL10 promoter, relieved by an IL32beta/PKCdelta-dependent change. Independent PMID:11672531 documents E2F repression and its requirement for differentiation in mouse genetic models. These support conserved contextual repression without making every CEBPA product or promoter repressive. The original electronic or similarity source remains unchanged. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11242107 Dominant-negative mutations of CEBPA, encoding CCAAT/enhance... | ACCEPT | Summary: Human WT CEBPA activates granulocyte target transcription. Reason: The original full PMID:11242107 reporter experiments establish activation of a CSF3R promoter by WT human CEBPA, with mutation- and p30-dependent differences. This is direct source support for the core transcriptional process; it does not imply equivalent activation by all four products. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12695546 Transcriptional regulation of human CYP3A4 basal expression ... | ACCEPT | Summary: CEBPA activates CYP3A4 transcription. Reason: The original abstract reports defined CEBPA-site mutations, reporter transactivation and increased endogenous CYP3A4 RNA after CEBPA overexpression. This supports the performed transcriptional step; the proposed chromatin-remodeling mechanism is not assigned as CEBPA catalytic activity. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20972335 Hypoxia-induced microRNA-424 expression in human endothelial... | ACCEPT | Summary: CEBPA participates in activation of a human endothelial transcriptional cascade. Reason: The original PMID:20972335 abstract and indexed Results report CEBPA/RUNX1-dependent PU.1 promoter output in human endothelial cells during hypoxia. Retain the transcriptional activity, without attributing all downstream miR424/HIF angiogenesis effects directly to CEBPA. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:7959007 NF-kappa B and C/EBP transcription factor families synergist... | ACCEPT | Summary: CEBPA can cooperate with NF-kappaB to activate a Pol II promoter. Reason: PMID:7959007 reports mouse SAA3-promoter reporters in Hep3B and F9 cells, with CEBPA alone giving marginal activation and cooperation producing stronger output. Preserve this source-specific combinatorial activity; the cache does not independently resolve the species of every expression plasmid. Human CEBPA activation is also established independently. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA positively regulates Pol II transcription. Reason: Retain the rat ortholog transfer, corroborated by human target promoter and endogenous expression experiments. The role is target- and partner-dependent rather than universal activation of all bound genes. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | ACCEPT | Summary: CEBPA cooperates with PU.1 and STAT3 to activate CCL2 transcription. Reason: Selected original full PMID:24429361 Results and Figures 3β4 show combined expression/knockdown, promoter reporters, ChIP and endogenous complex association in human hepatocytes. Preserve each original IGI partner. The performed CEBPA contribution is transcriptional regulation; co-IP does not prove an isolated binary contact. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | ACCEPT | Summary: CEBPA cooperates with PU.1 and STAT3 to activate CCL2 transcription. Reason: Selected original full PMID:24429361 Results and Figures 3β4 show combined expression/knockdown, promoter reporters, ChIP and endogenous complex association in human hepatocytes. Preserve each original IGI partner. The performed CEBPA contribution is transcriptional regulation; co-IP does not prove an isolated binary contact. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:16946298 STAT3 mediates hepatic hepcidin expression and its inflammat... | ACCEPT | Summary: CEBPA contributes to basal human HAMP transcription. Reason: The actual PMID:16946298 Figure 3 promoter-deletion and CEBPA-siRNA results support basal transcriptional activation in Huh7 cells. This is a CEBPA experiment within a STAT3-focused paper; no IL6-specific activator claim is substituted for the measured basal role. Supporting Evidence: |
| GO:0046982 protein heterodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: CEBPA heterodimerizes with other bZIP transcription factors. Reason: Human purified-domain interaction measurements, exact publisher target cells and curated complex records corroborate the conserved heterodimerization activity. Retain the activity as part of CEBPA transcription-factor architecture, without asserting that every measured pair has an established cellular target program. |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA can support a pro-inflammatory macrophage program. Reason: Full PMID:21131957 Results include Cebpa-specific conditional deletion and siRNA experiments, with reduced macrophage activation and inflammatory disease outcomes in mice. This supports the transferred process beyond miRNA-target correlation; the scope remains context-specific and is not generalized to every cytokine or tissue. Supporting Evidence: |
| GO:0050729 positive regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA can support a pro-inflammatory macrophage program. Reason: Full PMID:21131957 Results include Cebpa-specific conditional deletion and siRNA experiments, with reduced macrophage activation and inflammatory disease outcomes in mice. This supports the transferred process beyond miRNA-target correlation; the scope remains context-specific and is not generalized to every cytokine or tissue. Supporting Evidence: |
| GO:0051726 regulation of cell cycle | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | MODIFY | Summary: The cited CEBPA role restrains cell-cycle progression. Reason: The explicit CEBPA paragraph in the accessible original PMID:14685163 review describes CDK interaction/degradation and growth arrest. Independent E2F-repression mutants and CDK4-turnover experiments support a negative direction. Refine broad cell-cycle regulation to negative regulation of cell cycle; the CHOP-focused title is not evidence of a wrong-gene citation. Proposed replacements: negative regulation of cell cycle |
| GO:0055088 lipid homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA regulates hepatic lipid homeostasis through target transcription. Reason: PMID:17290224 reports mouse domain-selective knock-in effects on lipogenic promoters and hepatic lipid metabolism, including CEBPA/SREBP cooperation. Retain the physiological role with mouse-to-human scope explicit; CEBPA is a transcriptional regulator rather than a lipid-metabolic enzyme. Supporting Evidence: |
| GO:0055088 lipid homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA regulates hepatic lipid homeostasis through target transcription. Reason: PMID:17290224 reports mouse domain-selective knock-in effects on lipogenic promoters and hepatic lipid metabolism, including CEBPA/SREBP cooperation. Retain the physiological role with mouse-to-human scope explicit; CEBPA is a transcriptional regulator rather than a lipid-metabolic enzyme. Supporting Evidence: |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | KEEP AS NON CORE | Summary: CEBPA associates with the Pol II transcription factor PU.1. Reason: Original PMID:24429361 Figure 4D shows endogenous PU.1 co-immunoprecipitating with CEBPA from IL6-treated human hepatocytes, with IgG controls and promoter functional evidence. Retain the specific partner-class binding at complex-associated resolution, without claiming an isolated interface. Supporting Evidence: PMID:24429361 CEBPΞ±, PU.1, and STAT3 interacted with each other physically |
| GO:0070102 interleukin-6-mediated signaling pathway | IDA PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | KEEP AS NON CORE | Summary: CEBPA performs a transcriptional output of IL6 signaling. Reason: Original PMID:24429361 reporter, perturbation and ChIP experiments place CEBPA with PU.1/STAT3 in IL6-dependent CCL2 regulation in human hepatocytes. Retain this contextual pathway participation because CEBPA performs the transcriptional step, without assigning cytokine receptor or JAK kinase activity to it. Supporting Evidence: |
| GO:0070343 white fat cell proliferation | ISS PMID:36228616 Obesity caused by an OVOL2 mutation reveals dual roles of OV... | MODIFY | Summary: The OVOL2 study establishes CEBPA-dependent adipocyte differentiation. Reason: Selected full PMID:36228616 Figure 6 directly assays CEBPA reporter activity, DNA binding and adipogenic-promoter occupancy, while OVOL2 perturbation changes Oil Red O staining and adipogenic markers. These results support fat cell differentiation more directly than division of white fat cells. Preserve the original mouse similarity source and refine to the demonstrated differentiation process; no new annotation row is added. Proposed replacements: fat cell differentiation Supporting Evidence: PMID:36228616 OVOL2 blocks adipogenesis through direct inhibition of the transcriptional effects of C/EBPΞ±. |
| GO:0071837 HMG box domain binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA binds a Sox-family HMG-box region. Reason: The exact rat donor chain reaches PMID:16582099. Full Methods identify rat CEBPA coding sequence NM_012524; Results Figures 3β5 show its bZIP region interacting with Sox HMG regions in pull-down and co-IP assays. Binding was weak and salt-sensitive, and other HMG families did not show the same interaction. Retain the conserved domain-binding capability without generalizing to all HMG proteins or claiming direct human target experiments. |
| GO:0090575 RNA polymerase II transcription regulator complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CEBPA is a component of Pol II transcription-regulatory complexes. Reason: Retain the regulatory-complex annotation, independently corroborated by endogenous human CEBPAβPU.1βSTAT3 co-IP, target-promoter ChIP and functional reporter cooperation in PMID:24429361. The bZIP screens measure dimerization, not every cellular complex function, and the HAMP paper primarily measures promoter output rather than a purified complex. These source scopes remain distinct. |
| GO:0090575 RNA polymerase II transcription regulator complex | IMP PMID:16946298 STAT3 mediates hepatic hepcidin expression and its inflammat... | KEEP AS NON CORE | Summary: CEBPA is a component of Pol II transcription-regulatory complexes. Reason: Retain the regulatory-complex annotation, independently corroborated by endogenous human CEBPAβPU.1βSTAT3 co-IP, target-promoter ChIP and functional reporter cooperation in PMID:24429361. The bZIP screens measure dimerization, not every cellular complex function, and the HAMP paper primarily measures promoter output rather than a purified complex. These source scopes remain distinct. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | KEEP AS NON CORE | Summary: CEBPA is a component of Pol II transcription-regulatory complexes. Reason: Retain the regulatory-complex annotation, independently corroborated by endogenous human CEBPAβPU.1βSTAT3 co-IP, target-promoter ChIP and functional reporter cooperation in PMID:24429361. The bZIP screens measure dimerization, not every cellular complex function, and the HAMP paper primarily measures promoter output rather than a purified complex. These source scopes remain distinct. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | KEEP AS NON CORE | Summary: CEBPA is a component of Pol II transcription-regulatory complexes. Reason: Retain the regulatory-complex annotation, independently corroborated by endogenous human CEBPAβPU.1βSTAT3 co-IP, target-promoter ChIP and functional reporter cooperation in PMID:24429361. The bZIP screens measure dimerization, not every cellular complex function, and the HAMP paper primarily measures promoter output rather than a purified complex. These source scopes remain distinct. |
| GO:0097009 energy homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CEBPA contributes to energy homeostasis through regulated target-gene transcription. Reason: The mouse donor PMID:36977414 reports CEBPA-dependent leptin expression downstream of the succinate/SUCNR1 pathway, while mouse hepatic studies independently connect CEBPA domains to metabolic target expression. Retain this physiological regulatory role; it is distinct from the GO:0006091 chemical energy-generation claim and from direct nutrient sensing by CEBPA. |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CEBPA contributes to energy homeostasis through regulated target-gene transcription. Reason: The mouse donor PMID:36977414 reports CEBPA-dependent leptin expression downstream of the succinate/SUCNR1 pathway, while mouse hepatic studies independently connect CEBPA domains to metabolic target expression. Retain this physiological regulatory role; it is distinct from the GO:0006091 chemical energy-generation claim and from direct nutrient sensing by CEBPA. |
| GO:0097677 STAT family protein binding | IPI PMID:15664994 Signal transducers and activators of transcription 3 augment... | KEEP AS NON CORE | Summary: CEBPA associates with activated STAT3. Reason: The original PMID:15664994 abstract explicitly reports STAT3 binding and enhanced CEBPA transcriptional output in the G-CSF differentiation system. Retain the STAT-family binding activity while distinguishing the murine cellular context and unresolved individual-construct scope from independent human endogenous association in PMID:24429361. |
| GO:0097677 STAT family protein binding | IPI PMID:24429361 Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... | KEEP AS NON CORE | Summary: CEBPA associates with STAT3 in human hepatocytes. Reason: Selected full PMID:24429361 Results and Figure 4D show endogenous STAT3 co-immunoprecipitation with CEBPA after IL6 treatment, with IgG controls. Retain the specific binding activity at regulatory-complex resolution; neither isolated binary affinity nor STAT3 catalytic activity is inferred. Supporting Evidence: |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CEBPA interacts with other DNA-binding transcription factors. Reason: Direct bZIP dimerization and endogenous human PU.1/STAT3-associated complexes substantiate the electronic TF-binding assertion. Retain the general partner-class binding as non-core alongside the more precise dimerization activities. |
| GO:0140467 integrated stress response signaling | NAS PMID:28566324 Multi-omics analysis identifies ATF4 as a key regulator of t... | UNDECIDED | Summary: The specific CEBPA-containing complex contribution to the integrated stress response remains unresolved. Reason: The original full PMID:28566324 Results primarily establish ATF4-dependent mitochondrial stress responses. CPX-6525 genuinely contains CEBPA and ATF4 with this pathway citation, so this is a complex-context assertion, not an established wrong-gene error. Neither the inspected study nor the complex record resolves whether this particular heterodimer performs the ISR transcriptional step. Binding capacity alone does not establish that process. |
| GO:1990647 C/EBP complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: CEBPA forms C/EBP-family transcription-factor complexes. Reason: The original human bZIP target matrix and curated CEBPA-containing dimers support C/EBP complex membership. This complex architecture underlies sequence-specific transcriptional regulation; purified domain interactions are not used to assign every heterodimer an untested tissue-specific pathway. |
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Download this section (compressed HTML)Q: How do endogenous p42, p30 and the extended CEBPA product partition promoter and rDNA regulation in primary human myeloid cells?
Q: Which CEBPAβbZIP heterodimers occupy functional chromatin sites in human cells, particularly the ATF4-containing complex during integrated stress signaling?
Q: In which human cellular and product contexts does the reported direct CDK2/CDK4 inhibition contribute to growth restraint independently of transcriptional and E2F-regulatory mechanisms?
Experiment: Use product-selective endogenous tagging and perturbation in human myeloid progenitors, with matched chromatin occupancy, nascent Pol II RNA and rRNA measurements, to separate the shared bZIP activity from product-specific regulatory outputs.
Experiment: Measure CEBPA and ATF4 joint chromatin occupancy and transcriptional output under defined stress, with interface-selective rescue constructs that retain individual DNA-binding competence, to test the specific heterodimer contribution.
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