CEBP-2 is the C. elegans ortholog of mammalian CCAAT/enhancer-binding protein gamma (C/EBPgamma). It is a bZIP family transcription factor that functions as a key player in surveillance immunity, acting together with ZIP-2 in the protective response to translational block by P. aeruginosa Exotoxin A and perturbations of other core cellular processes. CEBP-2 also interacts with ZIP-11 to mediate innate immune responses independently of the PMK-1/p38 MAPK pathway. Beyond immunity, CEBP-2 regulates expression of genes involved in fat metabolism, controlling fatty acid mitochondrial beta-oxidation and desaturation. The protein is expressed broadly in somatic tissues including the intestine and localizes to the nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: CEBP-2 is a bZIP transcription factor that contains a basic DNA-binding region and leucine-zipper domain. The IBA annotation is based on phylogenetic inference from C/EBP family members that are established sequence-specific DNA-binding proteins. The UniProt entry confirms the bZIP domain (residues 17-80) with a basic motif (residues 23-48) and leucine-zipper (residues 52-73). Reason: This annotation is well-supported by domain architecture. CEBP-2 has a canonical bZIP domain with basic region for DNA binding. The C/EBP family is well characterized for sequence-specific DNA binding to CCAAT/enhancer elements. IBA annotations from PANTHER phylogenetic analysis are reliable for core transcription factor functions conserved across the family. Supporting Evidence: GO_REF:0000033 [Phylogenetic inference from C/EBP orthologs including mouse CEBPG, CEBPA, CEBPB, CEBPD, CEBPE, and human C/EBPgamma] file:worm/cebp-2/cebp-2-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: CEBP-2 regulates transcription as demonstrated by its role in controlling expression of immune response genes (irg-1), fat metabolism genes (ech-1.1, fat-5), and ESRE network genes upon P. aeruginosa infection. Reason: This is a core function of CEBP-2. Multiple publications demonstrate that CEBP-2 regulates transcription of target genes. PMID:26505800 shows CEBP-2 controls expression of ech-1.1 and fat-5. PMID:26876169 shows CEBP-2 is required for irg-1 activation. PMID:28662060 shows CEBP-2 is part of the bZIP transcription factor family regulating the ESRE network. Supporting Evidence: PMID:26876169 CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity PMID:26505800 loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: CEBP-2 functions as a DNA-binding transcription factor. It contains a bZIP domain and regulates transcription of target genes involved in immunity and metabolism. Reason: This is a core molecular function annotation. CEBP-2 has a canonical bZIP domain and functions as a transcription factor regulating gene expression. Experimental evidence from multiple studies demonstrates its transcriptional regulatory activity. Supporting Evidence: PMID:26876169 CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation based on UniProtKB keyword mapping. CEBP-2 has a well-established role in innate immunity based on experimental evidence. Reason: This annotation is supported by substantial experimental evidence. CEBP-2 is required for defense against P. aeruginosa infection and activates immune response genes. While the IEA evidence is computational, the annotation is accurate. The more specific annotation GO:0050829 (defense response to Gram-negative bacterium) is also present with experimental support. Supporting Evidence: PMID:26876169 CEBP-2 serves to limit pathogen burden, promote survival upon P. aeruginosa infection, and also promote survival upon Exotoxin A exposure |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProtKB keyword mapping. CEBP-2 contains a bZIP domain with a basic DNA-binding region. Reason: This is a valid annotation supported by domain architecture. However, the more specific annotation GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding) is also present and is more informative. Both annotations can be retained as the parent term is appropriate for IEA evidence level. Supporting Evidence: GO_REF:0000043 [UniProtKB keyword mapping for DNA-binding bZIP transcription factor] |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro domain mapping (IPR004827 bZIP, IPR031106 C/EBP, IPR046347 bZIP superfamily). CEBP-2 is a bZIP transcription factor. Reason: This annotation is accurate based on domain architecture and is consistent with the more specific GO:0000981 annotation. IEA annotations from InterPro are reliable for well-characterized domain families like bZIP. Supporting Evidence: GO_REF:0000002 [InterPro domain mapping for bZIP domain (IPR004827), C/EBP family (IPR031106), and bZIP superfamily (IPR046347)] |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProtKB subcellular location. CEBP-2 nuclear localization is also supported by direct experimental evidence. Reason: This annotation is accurate. CEBP-2 localizes to the nucleus as expected for a transcription factor. There are also IDA annotations for nucleus localization from PMID:34804026 and PMID:26876169 providing experimental confirmation. Supporting Evidence: GO_REF:0000044 [UniProtKB subcellular location vocabulary mapping for nucleus] |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated annotation methods. CEBP-2 is a transcription factor involved in DNA-templated transcription. Reason: This is a valid annotation. CEBP-2 is a transcription factor that regulates gene expression. The more specific GO:0006357 (regulation of transcription by RNA polymerase II) is also present. Both are appropriate. Supporting Evidence: GO_REF:0000120 [Combined automated annotation from InterPro and UniProtKB keywords] |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated annotation methods. CEBP-2 regulates transcription of target genes. Reason: This annotation is accurate and consistent with CEBP-2's function as a transcriptional regulator. The more specific GO:0006357 annotation with experimental evidence is also present. Supporting Evidence: GO_REF:0000120 [Combined automated annotation from InterPro domains and keywords] |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProtKB keyword mapping. CEBP-2 has a well-established role in innate immunity. Reason: This annotation is strongly supported by experimental evidence. CEBP-2 is required for defense against P. aeruginosa and functions in surveillance immunity together with ZIP-2 and ZIP-11. This is a core function. Supporting Evidence: PMID:26876169 CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity PMID:34804026 ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MARK AS OVER ANNOTATED | Summary: IPI annotation from bZIP protein-protein interaction network study. CEBP-2 was found to interact with multiple bZIP transcription factors including ATF-2, ATF-4, ATFS-1, CES-2, ZIP-2, ZIP-3, ZIP-9, and ZIP-11 as shown in the UniProt INTERACTION section. Reason: While the interactions are real, GO:0005515 (protein binding) is uninformative. The actual interactions are with specific bZIP transcription factors via leucine-zipper dimerization. A more specific term would be GO:0046983 (protein dimerization activity) or ideally annotations capturing the specific partners. However, as a general practice protein binding annotations from large-scale interaction studies have limited curation value. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs |
| GO:0005515 protein binding | IPI PMID:23791784 Extensive rewiring and complex evolutionary dynamics in a C.... | MARK AS OVER ANNOTATED | Summary: IPI annotation from C. elegans transcription factor network study characterizing protein-protein interactions. Reason: Same rationale as above - GO:0005515 is uninformative. The study characterized TF network rewiring but protein binding as an annotation provides little functional insight. Supporting Evidence: PMID:23791784 we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks |
| GO:0005515 protein binding | IPI PMID:34804026 The bZIP Transcription Factor ZIP-11 Is Required for the Inn... | MODIFY | Summary: IPI annotation for CEBP-2 interaction with ZIP-11 demonstrated by co-IP and validated in functional assays. Reason: The interaction with ZIP-11 is functionally significant - they work together to mediate immune responses. However, GO:0005515 is too vague. A more appropriate annotation would capture the dimerization activity characteristic of bZIP proteins. Proposed replacements: protein dimerization activity Supporting Evidence: PMID:34804026 ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection |
| GO:0005634 nucleus | IDA PMID:34804026 The bZIP Transcription Factor ZIP-11 Is Required for the Inn... | ACCEPT | Summary: Direct experimental evidence for CEBP-2 nuclear localization using GFP-tagged CEBP-2 reporter showing co-localization with ZIP-11 in intestinal nuclei upon P. aeruginosa infection. Reason: This is well-supported experimental evidence. The study used cebp-2p:: cebp-2::RFP transgenic worms and demonstrated nuclear localization in intestinal cells, especially upon pathogen exposure. Supporting Evidence: PMID:34804026 these two bZIP transcription factors exist noticeable co-localization in intestinal nucleus of worms upon P. aeruginosa infection |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:34804026 The bZIP Transcription Factor ZIP-11 Is Required for the Inn... | ACCEPT | Summary: IMP annotation based on genetic studies showing CEBP-2 is required for defense against P. aeruginosa PA14 infection. Loss of CEBP-2 reduces survival upon infection and the decrease in survival of zip-11 mutants is abolished by cebp-2 RNAi. Reason: This is a core function of CEBP-2. Multiple independent studies demonstrate CEBP-2 is required for defense against P. aeruginosa, a Gram-negative bacterium. This annotation is well-supported. Supporting Evidence: PMID:34804026 the decrease in survival upon P. aeruginosa infection of zip-11(tm4554) worms was abolished by cebp-2 RNAi |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:28662060 A conserved mitochondrial surveillance pathway is required f... | ACCEPT | Summary: IMP annotation from study demonstrating CEBP-2 is part of a conserved mitochondrial surveillance pathway required for defense against P. aeruginosa. CEBP-2 is one of the bZIP transcription factors mediating the ESRE (Ethanol and Stress Response Element) network involved in innate immunity. Reason: This annotation is strongly supported. The study shows CEBP-2 is part of the bZIP transcription factor family (along with ZIP-2, ZIP-4, CEBP-1) that mediates the ESRE defense network activated by P. aeruginosa infection. The cebp-2;zip-2 double mutant shows significantly more death than either single mutant upon P. aeruginosa exposure. Supporting Evidence: PMID:28662060 family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions ... The grey arrow indicates the cebp-2; zip-2 double mutant, which shows significantly more death than either single mutant |
| GO:0005634 nucleus | IDA PMID:26876169 The C. elegans CCAAT-Enhancer-Binding Protein Gamma Is Requi... | ACCEPT | Summary: Direct experimental evidence for nuclear localization using CEBP-2::GFP reporter in C. elegans intestinal cells. Reason: Well-supported IDA annotation. The study used GFP-tagged CEBP-2 to demonstrate nuclear localization in somatic tissues including the intestine. Supporting Evidence: PMID:26876169 CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:26505800 CCAAT/enhancer-binding protein CEBP-2 controls fat consumpti... | ACCEPT | Summary: IMP annotation based on CEBP-2 regulation of target genes ech-1.1 and fat-5 involved in fat metabolism. CEBP-2 mutants show altered expression of these transcriptional targets. Reason: This annotation is supported by experimental evidence showing CEBP-2 regulates transcription of fat metabolism genes. Mutations in cebp-2 result in altered expression of ech-1.1 (increased) and fat-5 (decreased), demonstrating its role as a transcriptional regulator. Supporting Evidence: PMID:26505800 loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5 ... cebp-2 controls total body fat content by governing fatty acid mitochondrial beta-oxidation and desaturation in C. elegans |
| GO:0019216 regulation of lipid metabolic process | IMP PMID:26505800 CCAAT/enhancer-binding protein CEBP-2 controls fat consumpti... | KEEP AS NON CORE | Summary: IMP annotation based on CEBP-2 regulation of fat consumption and fatty acid desaturation. CEBP-2 loss-of-function results in reduced overall fat content through effects on ech-1.1 and fat-5 gene expression. Reason: This is a real function of CEBP-2 supported by experimental evidence. However, the primary literature focus is on CEBP-2's role in immunity and surveillance pathways. The lipid metabolism function may represent a pleiotropic role or could be connected to immune metabolic reprogramming. Marking as non-core reflects that surveillance immunity appears to be the primary characterized function. Supporting Evidence: PMID:26505800 loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5 ... cebp-2 controls total body fat content by governing fatty acid mitochondrial beta-oxidation and desaturation in C. elegans |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:26876169 The C. elegans CCAAT-Enhancer-Binding Protein Gamma Is Requi... | ACCEPT | Summary: IMP annotation from the key study establishing CEBP-2's role in surveillance immunity. CEBP-2 is required for the protective response to P. aeruginosa infection and Exotoxin A exposure, acting together with ZIP-2. Reason: This is the seminal paper establishing CEBP-2 as a key player in surveillance immunity. CEBP-2 limits pathogen burden, promotes survival upon P. aeruginosa infection, and is required for irg-1 induction. This is a core function. Supporting Evidence: PMID:26876169 CEBP-2 serves to limit pathogen burden, promote survival upon P. aeruginosa infection, and also promote survival upon Exotoxin A exposure |
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Download this section (compressed HTML)Q: Does CEBP-2 directly bind to ESRE (Ethanol and Stress Response Element) motifs, or does it regulate ESRE network genes through a different mechanism?
Q: What is the relationship between CEBP-2's role in lipid metabolism and its immune function? Are these independent functions or interconnected through metabolic reprogramming during infection?
Experiment: ChIP-seq to identify direct CEBP-2 binding sites genome-wide and determine whether it binds CCAAT/enhancer elements and/or ESRE motifs.
Experiment: Epistasis analysis between cebp-2, zip-2, zip-11, and other bZIP factors during different types of stress (pathogen, mitochondrial, translational) to map the regulatory hierarchy.
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