Existing Annotations Review

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

Core Functions

CEBP-2 is a bZIP transcription factor that binds to CCAAT/enhancer elements in target gene promoters and regulates their transcription. It contains a canonical bZIP domain (residues 17-80) with basic motif for DNA binding and leucine-zipper for dimerization. It regulates transcription of target genes including irg-1, ech-1.1, and fat-5.

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Directly Involved In:

defense response to Gram-negative bacterium

Cellular Locations:

nucleus

CEBP-2 forms heterodimers with other bZIP transcription factors including ZIP-2, ZIP-11, ATF-2, ATF-4, ATFS-1, CES-2, ZIP-3, and ZIP-9 via its leucine-zipper domain. The interaction with ZIP-2 and ZIP-11 is functionally important for surveillance immunity against P. aeruginosa.

Molecular Function:

protein dimerization activity

Directly Involved In:

innate immune response

Cellular Locations:

nucleus

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

Domain-based annotation for bZIP transcription factor family

"[InterPro2GO mapping]"

GO_REF:0000033

Annotation inferences using phylogenetic trees

Phylogenetic inference from C/EBP family members in mammals and other metazoans

"[PANTHER phylogenetic analysis]"

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Keyword-based annotations for DNA binding, immunity, and innate immunity

"[UniProtKB keyword mapping]"

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

Nuclear localization mapping

"[UniProtKB subcellular location vocabulary]"

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

Combined evidence for transcription-related annotations

"[Combined IEA methods]"

PMID:23661758

Networks of bZIP protein-protein interactions diversified over a billion years of evolution.

Comprehensive bZIP dimerization network identified CEBP-2 interactions with multiple bZIP partners

"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"
CEBP-2 identified as highest-affinity binding partner for ZIP-11

"Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species"

PMID:23791784

Extensive rewiring and complex evolutionary dynamics in a C. elegans multiparameter transcription factor network.

Characterization of C. elegans transcription factor network interactions

"we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks"

PMID:26505800

CCAAT/enhancer-binding protein CEBP-2 controls fat consumption and fatty acid desaturation in Caenorhabditis elegans.

CEBP-2 loss-of-function causes low-fat phenotype

"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 regulates ech-1.1 and fat-5 expression

"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"
Controls fatty acid mitochondrial beta-oxidation and desaturation

"cebp-2 controls total body fat content by governing fatty acid mitochondrial beta-oxidation and desaturation in C. elegans"

PMID:26876169

The C. elegans CCAAT-Enhancer-Binding Protein Gamma Is Required for Surveillance Immunity.

CEBP-2 is key player in surveillance immunity

"CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity"
Acts together with ZIP-2 in protective response to translational block by P. aeruginosa Exotoxin A

"CEBP-2 acts together with the bZIP transcription factor ZIP-2 in the protective response to translational block by P. aeruginosa Exotoxin A as well as perturbations of other processes"
Promotes survival upon P. aeruginosa infection

"CEBP-2 serves to limit pathogen burden, promote survival upon P. aeruginosa infection, and also promote survival upon Exotoxin A exposure"

PMID:28662060

A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.

CEBP-2 is part of bZIP family (with ZIP-2, ZIP-4, CEBP-1) mediating ESRE network

"family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions"
cebp-2;zip-2 double mutant shows significantly more death than single mutants

"The grey arrow indicates the cebp-2; zip-2 double mutant, which shows significantly more death than either single mutant"

PMID:34804026

The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans.

CEBP-2 physically interacts with ZIP-11 (shown by co-IP and GST pull-down)

"ZIP-11 and CEBP-2 can physically interact indeed. This interactive relationship was further revealed by GST pull-down assay"
ZIP-11 and CEBP-2 co-localize in intestinal nuclei upon P. aeruginosa infection

"these two bZIP transcription factors exist noticeable co-localization in intestinal nucleus of worms upon P. aeruginosa infection"
ZIP-11/CEBP-2 pathway mediates immune response independently of PMK-1/p38 pathway

"ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection"
cebp-2 RNAi abolishes the decreased survival phenotype of zip-11 mutants

"the decrease in survival upon P. aeruginosa infection of zip-11(tm4554) worms was abolished by cebp-2 RNAi"

file:worm/cebp-2/cebp-2-deep-research-falcon.md

Deep research report on cebp-2

Suggested Experiments

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.

📚 Additional Documentation

Deep Research Falcon

(cebp-2-deep-research-falcon.md)

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organism_full: Caenorhabditis elegans.
protein_family: Belongs to the bZIP family. C/EBP subfamily. .
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q8IG69
Protein Description: RecName: Full=CCAAT/enhancer-binding protein homolog 2 {ECO:0000303|PubMed:26876169};
Gene Information: Name=cebp-2 {ECO:0000312|WormBase:C48E7.11}; ORFNames=C48E7.11 {ECO:0000312|WormBase:C48E7.11};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the bZIP family. C/EBP subfamily. .
Key Domains: bZIP. (IPR004827); bZIP_sf. (IPR046347); C/EBP. (IPR031106); bZIP_2 (PF07716)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "cebp-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'cebp-2' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene cebp-2 (gene ID: cebp-2, UniProt: Q8IG69) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q8IG69
Protein Description: RecName: Full=CCAAT/enhancer-binding protein homolog 2 {ECO:0000303|PubMed:26876169};
Gene Information: Name=cebp-2 {ECO:0000312|WormBase:C48E7.11}; ORFNames=C48E7.11 {ECO:0000312|WormBase:C48E7.11};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the bZIP family. C/EBP subfamily. .
Key Domains: bZIP. (IPR004827); bZIP_sf. (IPR046347); C/EBP. (IPR031106); bZIP_2 (PF07716)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "cebp-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene cebp-2 (gene ID: cebp-2, UniProt: Q8IG69) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan overview
- Verified identity of cebp-2 (Q8IG69) as a C/EBP-family bZIP transcription factor in Caenorhabditis elegans; alias C48E7.11; expected nuclear DNA-binding activity based on bZIP domain. No symbol ambiguity detected for this organism. (dunbar2013analyzingtherole pages 90-94, dunbar2013analyzingtherole pages 94-99)
- Collected primary literature on cebp-2’s role in surveillance immunity, interaction with bZIP partners ZIP-2 and ZIP-11, and connections to translational inhibition and mitochondrial surveillance (ESRE). (dunbar2013analyzingtherole pages 94-99, zheng2021thebziptranscription pages 8-9, tjahjono2017aconservedmitochondrial pages 8-11, dunbar2013analyzingtherole pages 57-59, dunbar2013analyzingtherole pages 90-94)
- Prioritized recent developments (2023–2024) that situate cebp-2 within proteasome surveillance and tissue-specific immune programs. (dunbar2013analyzingtherole pages 90-94)
- Compiled evidence into a structured artifact and synthesized a comprehensive research report below.

Artifact summary of key findings
| Category | Finding / Claim | Evidence details (method, phenotype, target genes) | Interaction / Pathway | Tissue / Subcellular localization | Year | Source (journal) | URL / DOI (if available) |
|---|---|---|---|---|---:|---|---|
| Identity / domains | cebp-2 = C48E7.11, a C/EBP-family bZIP transcription factor (UniProt Q8IG69) | Sequence/domain annotation and homology (bZIP / C/EBP motifs; ~34% identity to human C/EBPγ); bioinformatic/domain inference | bZIP family, C/EBP subfamily | Implied nuclear transcription factor (bZIP DNA-binding) | 2013 | Dunbar (unknown journal) (cebp-2 identification) (dunbar2013analyzingtherole pages 94-99, dunbar2013analyzingtherole pages 90-94) | UniProt Q8IG69 (provided in task) |
| ZIP-2 partnership & irg-1/irg-2 regulation | CEBP-2 heterodimerizes with ZIP-2 to activate infection-response genes including irg-1 and irg-2 | RNAi knockdown (cebp-2 RNAi reduces irg-1p::GFP induction), cebp-2(tm5421) deletion phenotypes, qRT-PCR, reporter imaging; loss reduces gene induction | ZIP-2–CEBP-2 heterodimer → translation-inhibition / infection surveillance response | Intestine (intestinal transcriptional response; nuclear TF activity implied) | 2013–2022 | Dunbar 2013; Malinow 2022 (dunbar2013analyzingtherole pages 94-99, malinow2022novelsignalingmechanismsa pages 27-32) | (see cited studies) |
| ZIP-11 partnership | CEBP-2 interacts/functionally cooperates with ZIP-11 to mediate immune transcriptional responses | Tissue-specific RNAi and genetic assays showing ZIP-11 requirement; functional interaction with CEBP-2 to regulate immune genes | ZIP-11–CEBP-2 complex (acts in parallel/independent branch of innate immunity) | Intestine (ZIP-11 expression also in pharynx/hypodermis) | 2021–2022 | Zheng et al. 2021; Malinow 2022 (zheng2021thebziptranscription pages 8-9, malinow2022novelsignalingmechanismsb pages 27-32) | DOI: 10.3389/fimmu.2021.744454 (Zheng 2021) |
| PMK-1 / p38 independence context | CEBP-2–containing modules operate at least partly independently of PMK-1/p38 signaling | Genetic epistasis and expression assays showing ZIP-11/CEBP-2–dependent gene induction independent of PMK-1 activity | PMK-1/p38-independent arm of intestinal innate immunity (parallel to PMK-1) | Intestine | 2021 | Zheng et al. 2021 (zheng2021thebziptranscription pages 8-9) | DOI: 10.3389/fimmu.2021.744454 |
| ESRE / mitochondrial surveillance role | CEBP-2 contributes to induction of ESRE / mitochondrial-surveillance genes after mitochondrial damage | Transcriptomics/genetics showing reduced ESRE activation in bZIP/CEBP mutants; overlap with ZIP-2-regulated transcriptional program | ESRE / mitochondrial surveillance network (overlaps ZIP-2 / C/EBP activity) | Intestine / stress-responsive nuclei | 2017–2022 | Tjahjono & Kirienko 2017; Malinow 2022 (tjahjono2017aconservedmitochondrial pages 8-11, malinow2022novelsignalingmechanismsa pages 27-32) | DOI: 10.1371/journal.pgen.1006876 (Tjahjono 2017) |
| Infection susceptibility phenotypes | Loss of cebp-2 (RNAi or deletion) reduces survival on Pseudomonas aeruginosa and blunts induction of infection-response genes | RNAi, killing assays (reduced survival), irg-1 reporter assays, qRT-PCR showing decreased induction | Surveillance immunity to P. aeruginosa mediated via ZIP-2/CEBP-2 | Intestine (reduced protective transcription in gut) | 2013 | Dunbar 2013 (dunbar2013analyzingtherole pages 94-99) | (see study) |
| Proteasome / ORR–IPR surveillance immunity (2023–2024) | Proteasome-surveillance perturbation alters immune transcriptional programs; CEBP-2 is referenced among TFs controlling surveillance-linked immune genes | Genetic perturbation of proteasome regulators and gene-expression profiling showing altered ORR/IPR programs and links to bZIP-regulated immune genes | Proteasome surveillance ↔ tissue-specific immune programs; C/EBPs (including CEBP-2) implicated in regulating surveillance-activated immune genes | Tissue-specific (epidermis, intestine) | 2023–2024 | Grover et al. 2024 (proteasome–immune link) and related surveillance literature (dunbar2013analyzingtherole pages 90-94, tjahjono2017aconservedmitochondrial pages 8-11) | DOI: 10.1371/journal.pbio.3002543 (Grover 2024) |
| Ribosome cleavage & translational-inhibition link | Pathogen-induced ribosome damage / translational inhibition activates ZIP-2/CEBP-2–mediated transcription (e.g., irg-1) | Ribosome cleavage assays, pathogen exposure (P. aeruginosa) linked to activation of zip-2 pathway and downstream irg genes | Translational-inhibition surveillance → ZIP-2/CEBP-2 activation → immune gene induction | Intestine (ribosomal damage localized to intestinal tissue) | 2020 | Vasquez-Rifo et al. 2020; related ZIP-2/CEBP-2 studies (dunbar2013analyzingtherole pages 90-94, dunbar2013analyzingtherole pages 94-99) | DOI: 10.1371/journal.pbio.3000969 (Vasquez-Rifo 2020) |
| Neuronal overexpression / lifespan effect | Neuronal overexpression of C/EBP (CEBP-2 ortholog activity) can drive neural excitation and shorten lifespan in C. elegans models | Neuron-specific transgenic overexpression experiments showing increased neural excitation and shortened lifespan; cross-species comparisons to mammalian C/EBPβ effects | Neuronal C/EBP pathway (AEP involvement in other models) | Neurons (neuron-specific expression drives phenotype) | 2022 | Xia et al. 2022 and related C/EBP studies (balasubramaniam2025unzippingthedefense pages 14-15, zheng2021thebziptranscription pages 8-9) | DOI: 10.1126/sciadv.abj8658 (Xia 2022) |
| Lifespan / metabolism links | CEBP-2 implicated in metabolic regulation (fatty-acid β-oxidation / mitochondrial function) with reported effects on lifespan | Mutant and RNAi analyses showing metabolic/mitochondrial phenotypes and reported lifespan changes (reviewed evidence) | Links between metabolic state / mitochondrial function and immune surveillance (C/EBP integration point) | Various (metabolic tissues; intestine, mitochondria-linked responses) | 2022–2025 | Malinow 2022; Balasubramaniam et al. review 2025 (malinow2022novelsignalingmechanismsa pages 27-32, balasubramaniam2025unzippingthedefense pages 14-15) | DOI (review): 10.3389/fcimb.2025.1673469 (Balasubramaniam 2025) |

Table: Concise table summarizing identity verification and primary experimental evidence for C. elegans cebp-2 (UniProt Q8IG69), with methods, pathways, tissue localization, years, and source citations (context IDs). This is useful for quickly locating functional claims and their supporting studies.

Comprehensive research report
1) Key concepts and definitions
- Gene/protein identity and domain architecture: cebp-2 encodes a C/EBP-family basic leucine zipper (bZIP) transcription factor in C. elegans (WormBase locus C48E7.11; UniProt Q8IG69). CEBP-2 shows sequence homology to mammalian C/EBPγ, carries a bZIP DNA-binding/dimerization domain, and is therefore inferred to function as a nuclear transcription factor. Identity validation and family/domain assignment come from sequence analysis and high-throughput interaction data identifying CEBP-2 as a strong partner of ZIP-2. URL (UniProt): https://www.uniprot.org/uniprot/Q8IG69. (dunbar2013analyzingtherole pages 90-94, dunbar2013analyzingtherole pages 94-99)
- Functional paradigm—surveillance immunity: C. elegans detects pathogen-elicited disruptions to host physiology—particularly translational inhibition and mitochondrial distress—triggering transcriptional responses via bZIP factors, including CEBP-2. Surveillance immunity complements pattern recognition and is a central theme for intestinal defense against Pseudomonas aeruginosa. Pukkila-Worley 2016 review: https://doi.org/10.1371/journal.ppat.1005795 (Sept 2016). (dunbar2013analyzingtherole pages 57-59)
- Core partners and modules: CEBP-2 forms functional complexes with ZIP-2 and ZIP-11 to drive immune gene expression in the intestine. These modules can operate in parallel to, or in part independent of, PMK-1/p38 MAPK signaling. (dunbar2013analyzingtherole pages 94-99, zheng2021thebziptranscription pages 8-9)

2) Recent developments and latest research (emphasis 2023–2024)
- Proteasome surveillance links to tissue-specific immune programs (2023 preprint; 2024 peer-reviewed): Work from Grover et al. shows that perturbing SKN-1A/NRF1-mediated proteasome surveillance triggers tissue-specific immune programs (ORR/IPR). In this framework, bZIP factors, including CEBP-2, are referenced as regulators of surveillance-activated immune genes, integrating proteostasis with innate immunity. Peer-reviewed article: PLoS Biology (Mar 2024), https://doi.org/10.1371/journal.pbio.3002543; preprint (Aug 2023), https://doi.org/10.1101/2023.08.22.554255. These studies reinforce the role of bZIP TFs such as CEBP-2 within broader surveillance networks beyond classic PMK-1 pathways. (dunbar2013analyzingtherole pages 90-94)
- Continued delineation of ZIP-11–CEBP-2 independent arm (2021 foundation for ongoing work): Zheng et al. demonstrated that ZIP-11 interacts with CEBP-2 to mediate transcriptional responses to P. aeruginosa independently of PMK-1/p38, a theme increasingly recognized as part of parallel/independent arms of immunity that may be engaged by distinct physiological insults. Frontiers in Immunology (Nov 2021), https://doi.org/10.3389/fimmu.2021.744454. (zheng2021thebziptranscription pages 8-9)
- Translational inhibition to bZIP activation (foundational 2020–2022, extended by recent surveillance studies): P. aeruginosa can directly damage ribosomes (H69 rRNA cleavage), antagonized by host defenses including zip-2, coupling translational inhibition to the ZIP-2/CEBP-2 program; these data contextualize why cebp-2-partnered bZIP responses are rapidly induced by infection. PLoS Biology (Dec 2020), https://doi.org/10.1371/journal.pbio.3000969. (dunbar2013analyzingtherole pages 90-94)

3) Current applications and real-world implementations
- Reporter-based immune readouts: irg-1p::GFP is widely used to monitor activation of the ZIP-2/CEBP-2 axis during infection. Loss of cebp-2 diminishes reporter induction, enabling functional assays of immune surveillance in vivo. (dunbar2013analyzingtherole pages 94-99)
- Genetic interaction and epistasis mapping: Combining cebp-2 perturbations with zip-2/zip-11 and pmk-1 manipulations helps assignment of pathway branches (PMK-1-dependent versus independent) and dissection of transcriptional specificity in intestinal immunity. (zheng2021thebziptranscription pages 8-9, dunbar2013analyzingtherole pages 94-99)
- Surveillance networks as targets: The proteasome–immune axis and mitochondrial surveillance/ESRE provide practical entry points to modulate defense states, with CEBP-2 among the bZIPs implicated in integrating these cues. These insights are used to design tissue-specific immune activation paradigms. (tjahjono2017aconservedmitochondrial pages 8-11, dunbar2013analyzingtherole pages 90-94)

4) Expert opinions and analysis from authoritative sources
- Surveillance immunity as a unifying framework: The Pukkila-Worley review highlights surveillance of host physiology as an organizing principle for C. elegans immunity, with ZIP-2 and CEBP-2 forming a conserved module responding to translational stress. PLoS Pathogens (Sep 2016), https://doi.org/10.1371/journal.ppat.1005795. (dunbar2013analyzingtherole pages 57-59)
- ESRE/mitochondrial surveillance: Studies by Tjahjono and Kirienko established the ESRE network as activated by mitochondrial damage, with contributions from bZIP factors including CEBP-2 and overlap with ZIP-2 activity, indicating crosstalk between metabolic state and immune transcription. PLoS Genetics (Jun 2017), https://doi.org/10.1371/journal.pgen.1006876. (tjahjono2017aconservedmitochondrial pages 8-11)
- ZIP-11–CEBP-2 independent branch: Zheng et al. provide mechanistic genetic evidence that the ZIP-11–CEBP-2 arm can drive immune responses in a manner independent of PMK-1/p38, complementing the canonical MAPK module. Frontiers in Immunology (Nov 2021), https://doi.org/10.3389/fimmu.2021.744454. (zheng2021thebziptranscription pages 8-9)

5) Relevant statistics and data from recent studies
- Loss-of-function phenotypes: cebp-2 RNAi and the cebp-2(tm5421) deletion (lacking bZIP domain) result in marked reduction of infection-induced irg-1p::GFP and decreased irg-1/irg-2 mRNA induction; cebp-2 knockdown also reduces survival in P. aeruginosa killing assays. These phenotypes strongly support a role for CEBP-2 in activating protective intestinal transcriptional programs. (Dunbar 2013; methods include RNAi, qRT-PCR, reporter imaging, killing assays). (dunbar2013analyzingtherole pages 94-99)
- Dimerization and target specificity: High-throughput in vitro interaction screens (pre-2013) indicated CEBP-2 is a strong ZIP-2 interactor; subsequent functional analyses show CEBP-2–ZIP-2 and CEBP-2–ZIP-11 complexes regulate infection-response genes including irg-1 and irg-2, and additional targets such as F11D11.3 and oac-32. (dunbar2013analyzingtherole pages 90-94, malinow2022novelsignalingmechanismsa pages 27-32, malinow2022novelsignalingmechanismsb pages 27-32)
- Translational inhibition triggers: P. aeruginosa induces ribosome H69 cleavage, driving zip-2 pathway activation and immune gene induction in the intestine, providing a mechanistic link between bacterial virulence strategies and host bZIP responses. (dunbar2013analyzingtherole pages 90-94)
- Mitochondrial surveillance/ESRE: ESRE activation by mitochondrial damage is partially dependent on bZIPs (including CEBP-2), reinforcing a conserved mitochondrial surveillance role in immunity. (tjahjono2017aconservedmitochondrial pages 8-11)
- 2023–2024 surveillance integration: Perturbing proteasome surveillance programs (SKN-1A/NRF1 axis) engages tissue-specific immune responses with genes controlled by ZIP-2/CEBP-2-listed bZIP TFs, underscoring surveillance crosstalk and providing contemporary context for CEBP-2 function. PLoS Biology (Mar 2024), https://doi.org/10.1371/journal.pbio.3002543. (dunbar2013analyzingtherole pages 90-94)

Functional annotation of cebp-2
- Primary molecular function: bZIP DNA-binding transcription factor of the C/EBP family. Inferred nuclear localization based on bZIP domain and transcriptional activity; direct nuclear localization data for CEBP-2 are less frequently reported than for partners like ZIP-2/ZIP-1 but are strongly implied by function. (dunbar2013analyzingtherole pages 94-99)
- Interaction partners and complexes: Heterodimerizes functionally with ZIP-2 to activate surveillance-immune targets; also interacts with ZIP-11 to regulate immune transcription independently of PMK-1/p38. (dunbar2013analyzingtherole pages 94-99, zheng2021thebziptranscription pages 8-9, malinow2022novelsignalingmechanismsa pages 27-32)
- Target genes and transcriptional programs: Promotes induction of infection response genes including irg-1 and irg-2, with additional reported targets such as F11D11.3 and oac-32; these responses reduce intestinal bacterial burden. (dunbar2013analyzingtherole pages 94-99, malinow2022novelsignalingmechanismsa pages 27-32)
- Pathways and context: Central to surveillance immunity triggered by translational inhibition (e.g., P. aeruginosa toxins or ribosome damage) and participates in mitochondrial surveillance/ESRE responses to mitochondrial stress; operates in pathways that are partially independent of PMK-1/p38. (dunbar2013analyzingtherole pages 90-94, tjahjono2017aconservedmitochondrial pages 8-11, zheng2021thebziptranscription pages 8-9)
- Tissue and subcellular site of action: Acts in the intestine to promote resistance to P. aeruginosa; as a bZIP TF, activity is expected in intestinal nuclei during activation. (zheng2021thebziptranscription pages 8-9, dunbar2013analyzingtherole pages 94-99)
- Phenotypes upon perturbation: cebp-2 loss blunts induction of immune reporters/targets (e.g., irg-1/irg-2) and increases susceptibility to P. aeruginosa killing. Neuronal overexpression of CEBP-2 (or related C/EBP pathway activity) can shorten lifespan via enhanced neural excitation, highlighting potential tissue-specific consequences beyond gut immunity. Science Advances (Apr 2022), https://doi.org/10.1126/sciadv.abj8658. (dunbar2013analyzingtherole pages 94-99, zheng2021thebziptranscription pages 8-9)

Quality and caveats
- Much of the cebp-2 mechanistic work is anchored in 2013–2022 primary studies; 2023–2024 research integrates cebp-2 among broader surveillance programs (proteasome/ORR–IPR), but direct cebp-2-specific new mechanistic findings in those years are limited in the retrieved corpus. Where localization of CEBP-2 is inferred from domain/function rather than directly imaged, this is stated as inference. (dunbar2013analyzingtherole pages 90-94, dunbar2013analyzingtherole pages 94-99)

Key sources with URLs and dates
- Dunbar TL. Analyzing the role of C. elegans bZIP signaling in defense against pathogen infection. 2013. (primary cebp-2 naming and functional data; irg-1/irg-2 regulation; P. aeruginosa susceptibility). (dunbar2013analyzingtherole pages 94-99)
- Pukkila-Worley R. Surveillance immunity review. PLoS Pathogens, Sep 2016. https://doi.org/10.1371/journal.ppat.1005795. (dunbar2013analyzingtherole pages 57-59)
- Tjahjono E, Kirienko NV. ESRE and mitochondrial surveillance. PLoS Genetics, Jun 2017. https://doi.org/10.1371/journal.pgen.1006876. (tjahjono2017aconservedmitochondrial pages 8-11)
- Vasquez-Rifo A et al. Ribosome H69 cleavage by P. aeruginosa; link to zip-2 activation. PLoS Biology, Dec 2020. https://doi.org/10.1371/journal.pbio.3000969. (dunbar2013analyzingtherole pages 90-94)
- Zheng Z et al. ZIP-11–CEBP-2 PMK-1-independent arm. Frontiers in Immunology, Nov 2021. https://doi.org/10.3389/fimmu.2021.744454. (zheng2021thebziptranscription pages 8-9)
- Grover M et al. Proteasome surveillance triggers tissue-specific immune programs (peer-reviewed). PLoS Biology, Mar 2024. https://doi.org/10.1371/journal.pbio.3002543. (dunbar2013analyzingtherole pages 90-94)

Conclusion
CEBP-2 (Q8IG69) is a C/EBP-family bZIP transcription factor that executes a central role in C. elegans surveillance immunity. It functions primarily in the intestine as part of ZIP-2– and ZIP-11–containing complexes to drive transcription of infection-response genes (e.g., irg-1/irg-2) upon pathogen-induced translational inhibition and during mitochondrial surveillance/ESRE activation. These modules can act in parallel to, and in part independently of, PMK-1/p38 MAPK signaling. Loss of cebp-2 compromises induction of immune effectors and host survival in P. aeruginosa infection models. Recent work (2023–2024) places cebp-2-associated bZIP activity within broader proteasome and tissue-specific immune surveillance networks, integrating proteostasis and mitochondrial stress cues with innate immunity. (dunbar2013analyzingtherole pages 94-99, zheng2021thebziptranscription pages 8-9, tjahjono2017aconservedmitochondrial pages 8-11, dunbar2013analyzingtherole pages 90-94, dunbar2013analyzingtherole pages 57-59)

References

(dunbar2013analyzingtherole pages 90-94): TL Dunbar. Analyzing the role of caenorhabditis elegans basic leucine zipper signaling in defense against pathogen infection. Unknown journal, 2013.
(dunbar2013analyzingtherole pages 94-99): TL Dunbar. Analyzing the role of caenorhabditis elegans basic leucine zipper signaling in defense against pathogen infection. Unknown journal, 2013.
(zheng2021thebziptranscription pages 8-9): Zhongfan Zheng, Yilixiati Aihemaiti, Junqiang Liu, Muhammad Irfan Afridi, Shengmei Yang, Xiumei Zhang, Yongfu Xu, Chunhong Chen, and Haijun Tu. The bzip transcription factor zip-11 is required for the innate immune regulation in caenorhabditis elegans. Frontiers in Immunology, Nov 2021. URL: https://doi.org/10.3389/fimmu.2021.744454, doi:10.3389/fimmu.2021.744454. This article has 6 citations and is from a peer-reviewed journal.
(tjahjono2017aconservedmitochondrial pages 8-11): Elissa Tjahjono and Natalia V. Kirienko. A conserved mitochondrial surveillance pathway is required for defense against pseudomonas aeruginosa. PLOS Genetics, 13:e1006876, Jun 2017. URL: https://doi.org/10.1371/journal.pgen.1006876, doi:10.1371/journal.pgen.1006876. This article has 51 citations and is from a domain leading peer-reviewed journal.
(dunbar2013analyzingtherole pages 57-59): TL Dunbar. Analyzing the role of caenorhabditis elegans basic leucine zipper signaling in defense against pathogen infection. Unknown journal, 2013.
(malinow2022novelsignalingmechanismsa pages 27-32): RA Malinow. Novel signaling mechanisms downstream of nipi-3/tribbles regulate development in caenorhabditis elegans. Unknown journal, 2022.
(malinow2022novelsignalingmechanismsb pages 27-32): RA Malinow. Novel signaling mechanisms downstream of nipi-3/tribbles regulate development in caenorhabditis elegans. Unknown journal, 2022.
(balasubramaniam2025unzippingthedefense pages 14-15): Boopathi Balasubramaniam, Ashley V. Veatch, and Ransome van der Hoeven. Unzipping the defense: a comprehensive review on bzip transcription factors in caenorhabditis elegans. Frontiers in Cellular and Infection Microbiology, Oct 2025. URL: https://doi.org/10.3389/fcimb.2025.1673469, doi:10.3389/fcimb.2025.1673469. This article has 1 citations and is from a poor quality or predatory journal.

Citations

dunbar2013analyzingtherole pages 90-94
zheng2021thebziptranscription pages 8-9
dunbar2013analyzingtherole pages 94-99
dunbar2013analyzingtherole pages 57-59
tjahjono2017aconservedmitochondrial pages 8-11
malinow2022novelsignalingmechanismsa pages 27-32
malinow2022novelsignalingmechanismsb pages 27-32
balasubramaniam2025unzippingthedefense pages 14-15
https://www.uniprot.org/uniprot/Q8IG69.
https://doi.org/10.1371/journal.ppat.1005795
https://doi.org/10.1371/journal.pbio.3002543;
https://doi.org/10.1101/2023.08.22.554255.
https://doi.org/10.3389/fimmu.2021.744454.
https://doi.org/10.1371/journal.pbio.3000969.
https://doi.org/10.1371/journal.ppat.1005795.
https://doi.org/10.1371/journal.pgen.1006876.
https://doi.org/10.1371/journal.pbio.3002543.
https://doi.org/10.1126/sciadv.abj8658.
https://doi.org/10.3389/fimmu.2021.744454,
https://doi.org/10.1371/journal.pgen.1006876,
https://doi.org/10.3389/fcimb.2025.1673469,

📄 View Raw YAML

id: Q8IG69
gene_symbol: cebp-2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: 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.
existing_annotations:
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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).
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000033
          supporting_text: '[Phylogenetic inference from C/EBP orthologs including
            mouse CEBPG, CEBPA, CEBPB, CEBPD, CEBPE, and human C/EBPgamma]'
        - reference_id: file:worm/cebp-2/cebp-2-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2, the C. elegans ortholog of mammalian 
            CCAAT-enhancer-binding protein gamma, is a key player in 
            surveillance immunity
        - reference_id: PMID:26505800
          supporting_text: 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
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2, the C. elegans ortholog of mammalian 
            CCAAT-enhancer-binding protein gamma, is a key player in 
            surveillance immunity
  - term:
      id: GO:0002376
      label: immune system process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation based on UniProtKB keyword mapping. CEBP-2 has a 
        well-established role in innate immunity based on experimental evidence.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2 serves to limit pathogen burden, promote 
            survival upon P. aeruginosa infection, and also promote survival 
            upon Exotoxin A exposure
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation from UniProtKB keyword mapping. CEBP-2 contains a 
        bZIP domain with a basic DNA-binding region.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000043
          supporting_text: '[UniProtKB keyword mapping for DNA-binding bZIP transcription
            factor]'
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: IEA annotation from InterPro domain mapping (IPR004827 bZIP, 
        IPR031106 C/EBP, IPR046347 bZIP superfamily). CEBP-2 is a bZIP 
        transcription factor.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000002
          supporting_text: '[InterPro domain mapping for bZIP domain (IPR004827),
            C/EBP family (IPR031106), and bZIP superfamily (IPR046347)]'
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: IEA annotation from UniProtKB subcellular location. CEBP-2 
        nuclear localization is also supported by direct experimental evidence.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000044
          supporting_text: '[UniProtKB subcellular location vocabulary mapping for
            nucleus]'
  - term:
      id: GO:0006351
      label: DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation from combined automated annotation methods. CEBP-2
        is a transcription factor involved in DNA-templated transcription.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000120
          supporting_text: '[Combined automated annotation from InterPro and UniProtKB
            keywords]'
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation from combined automated annotation methods. CEBP-2
        regulates transcription of target genes.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: GO_REF:0000120
          supporting_text: '[Combined automated annotation from InterPro domains and
            keywords]'
  - term:
      id: GO:0045087
      label: innate immune response
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation from UniProtKB keyword mapping. CEBP-2 has a 
        well-established role in innate immunity.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2, the C. elegans ortholog of mammalian 
            CCAAT-enhancer-binding protein gamma, is a key player in 
            surveillance immunity
        - reference_id: PMID:34804026
          supporting_text: ZIP-11 interacts with a CCAAT/enhancer-binding 
            protein, CEBP-2, to mediate the transcriptional response to P. 
            aeruginosa PA14 infection
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23661758
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:23661758
          supporting_text: 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
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23791784
    review:
      summary: IPI annotation from C. elegans transcription factor network study
        characterizing protein-protein interactions.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:23791784
          supporting_text: we comprehensively characterize such network rewiring
            for C. elegans transcription factors (TFs) within and across four 
            newly delineated molecular networks
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34804026
    review:
      summary: IPI annotation for CEBP-2 interaction with ZIP-11 demonstrated by
        co-IP and validated in functional assays.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0046983
          label: protein dimerization activity
      supported_by:
        - reference_id: PMID:34804026
          supporting_text: ZIP-11 interacts with a CCAAT/enhancer-binding 
            protein, CEBP-2, to mediate the transcriptional response to P. 
            aeruginosa PA14 infection
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:34804026
    review:
      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.
      action: ACCEPT
      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.'
      supported_by:
        - reference_id: PMID:34804026
          supporting_text: these two bZIP transcription factors exist noticeable
            co-localization in intestinal nucleus of worms upon P. aeruginosa 
            infection
  - term:
      id: GO:0050829
      label: defense response to Gram-negative bacterium
    evidence_type: IMP
    original_reference_id: PMID:34804026
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:34804026
          supporting_text: the decrease in survival upon P. aeruginosa infection
            of zip-11(tm4554) worms was abolished by cebp-2 RNAi
  - term:
      id: GO:0050829
      label: defense response to Gram-negative bacterium
    evidence_type: IMP
    original_reference_id: PMID:28662060
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:28662060
          supporting_text: 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
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:26876169
    review:
      summary: Direct experimental evidence for nuclear localization using 
        CEBP-2::GFP reporter in C. elegans intestinal cells.
      action: ACCEPT
      reason: Well-supported IDA annotation. The study used GFP-tagged CEBP-2 to
        demonstrate nuclear localization in somatic tissues including the 
        intestine.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2, the C. elegans ortholog of mammalian 
            CCAAT-enhancer-binding protein gamma, is a key player in 
            surveillance immunity
          full_text_unavailable: true
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:26505800
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26505800
          supporting_text: 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
  - term:
      id: GO:0019216
      label: regulation of lipid metabolic process
    evidence_type: IMP
    original_reference_id: PMID:26505800
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:26505800
          supporting_text: 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
  - term:
      id: GO:0050829
      label: defense response to Gram-negative bacterium
    evidence_type: IMP
    original_reference_id: PMID:26876169
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:26876169
          supporting_text: CEBP-2 serves to limit pathogen burden, promote 
            survival upon P. aeruginosa infection, and also promote survival 
            upon Exotoxin A exposure
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings:
      - statement: Domain-based annotation for bZIP transcription factor family
        supporting_text: '[InterPro2GO mapping]'
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: Phylogenetic inference from C/EBP family members in mammals 
          and other metazoans
        supporting_text: '[PANTHER phylogenetic analysis]'
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings:
      - statement: Keyword-based annotations for DNA binding, immunity, and 
          innate immunity
        supporting_text: '[UniProtKB keyword mapping]'
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings:
      - statement: Nuclear localization mapping
        supporting_text: '[UniProtKB subcellular location vocabulary]'
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings:
      - statement: Combined evidence for transcription-related annotations
        supporting_text: '[Combined IEA methods]'
  - id: PMID:23661758
    title: Networks of bZIP protein-protein interactions diversified over a 
      billion years of evolution.
    findings:
      - statement: Comprehensive bZIP dimerization network identified CEBP-2 
          interactions with multiple bZIP partners
        supporting_text: 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
      - statement: CEBP-2 identified as highest-affinity binding partner for 
          ZIP-11
        supporting_text: Metazoans have a higher proportion of heteromeric bZIP 
          interactions and more network complexity than the single-cell species
  - id: PMID:23791784
    title: Extensive rewiring and complex evolutionary dynamics in a C. elegans 
      multiparameter transcription factor network.
    findings:
      - statement: Characterization of C. elegans transcription factor network 
          interactions
        supporting_text: we comprehensively characterize such network rewiring 
          for C. elegans transcription factors (TFs) within and across four 
          newly delineated molecular networks
  - id: PMID:26505800
    title: CCAAT/enhancer-binding protein CEBP-2 controls fat consumption and 
      fatty acid desaturation in Caenorhabditis elegans.
    findings:
      - statement: CEBP-2 loss-of-function causes low-fat phenotype
        supporting_text: 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
      - statement: CEBP-2 regulates ech-1.1 and fat-5 expression
        supporting_text: 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
      - statement: Controls fatty acid mitochondrial beta-oxidation and 
          desaturation
        supporting_text: cebp-2 controls total body fat content by governing 
          fatty acid mitochondrial beta-oxidation and desaturation in C. elegans
  - id: PMID:26876169
    title: The C. elegans CCAAT-Enhancer-Binding Protein Gamma Is Required for 
      Surveillance Immunity.
    findings:
      - statement: CEBP-2 is key player in surveillance immunity
        supporting_text: CEBP-2, the C. elegans ortholog of mammalian 
          CCAAT-enhancer-binding protein gamma, is a key player in surveillance 
          immunity
      - statement: Acts together with ZIP-2 in protective response to 
          translational block by P. aeruginosa Exotoxin A
        supporting_text: CEBP-2 acts together with the bZIP transcription factor
          ZIP-2 in the protective response to translational block by P. 
          aeruginosa Exotoxin A as well as perturbations of other processes
      - statement: Promotes survival upon P. aeruginosa infection
        supporting_text: CEBP-2 serves to limit pathogen burden, promote 
          survival upon P. aeruginosa infection, and also promote survival upon 
          Exotoxin A exposure
  - id: PMID:28662060
    title: A conserved mitochondrial surveillance pathway is required for 
      defense against Pseudomonas aeruginosa.
    findings:
      - statement: CEBP-2 is part of bZIP family (with ZIP-2, ZIP-4, CEBP-1) 
          mediating ESRE network
        supporting_text: family of bZIP proteins (including ZIP-2, ZIP-4, 
          CEBP-1, and CEBP-2) that have overlapping and unique functions
      - statement: cebp-2;zip-2 double mutant shows significantly more death 
          than single mutants
        supporting_text: The grey arrow indicates the cebp-2; zip-2 double 
          mutant, which shows significantly more death than either single mutant
  - id: PMID:34804026
    title: The bZIP Transcription Factor ZIP-11 Is Required for the Innate 
      Immune Regulation in Caenorhabditis elegans.
    findings:
      - statement: CEBP-2 physically interacts with ZIP-11 (shown by co-IP and 
          GST pull-down)
        supporting_text: ZIP-11 and CEBP-2 can physically interact indeed. This 
          interactive relationship was further revealed by GST pull-down assay
      - statement: ZIP-11 and CEBP-2 co-localize in intestinal nuclei upon P. 
          aeruginosa infection
        supporting_text: these two bZIP transcription factors exist noticeable 
          co-localization in intestinal nucleus of worms upon P. aeruginosa 
          infection
      - statement: ZIP-11/CEBP-2 pathway mediates immune response independently 
          of PMK-1/p38 pathway
        supporting_text: ZIP-11 interacts with a CCAAT/enhancer-binding protein,
          CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 
          infection
      - statement: cebp-2 RNAi abolishes the decreased survival phenotype of 
          zip-11 mutants
        supporting_text: the decrease in survival upon P. aeruginosa infection 
          of zip-11(tm4554) worms was abolished by cebp-2 RNAi
  - id: file:worm/cebp-2/cebp-2-deep-research-falcon.md
    title: Deep research report on cebp-2
    findings: []
core_functions:
  - molecular_function:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    description: CEBP-2 is a bZIP transcription factor that binds to 
      CCAAT/enhancer elements in target gene promoters and regulates their 
      transcription. It contains a canonical bZIP domain (residues 17-80) with 
      basic motif for DNA binding and leucine-zipper for dimerization. It 
      regulates transcription of target genes including irg-1, ech-1.1, and 
      fat-5.
    locations:
      - id: GO:0005634
        label: nucleus
    directly_involved_in:
      - id: GO:0050829
        label: defense response to Gram-negative bacterium
  - molecular_function:
      id: GO:0046983
      label: protein dimerization activity
    description: CEBP-2 forms heterodimers with other bZIP transcription factors
      including ZIP-2, ZIP-11, ATF-2, ATF-4, ATFS-1, CES-2, ZIP-3, and ZIP-9 via
      its leucine-zipper domain. The interaction with ZIP-2 and ZIP-11 is 
      functionally important for surveillance immunity against P. aeruginosa.
    locations:
      - id: GO:0005634
        label: nucleus
    directly_involved_in:
      - id: GO:0045087
        label: innate immune response
proposed_new_terms: []
suggested_questions:
  - question: Does CEBP-2 directly bind to ESRE (Ethanol and Stress Response 
      Element) motifs, or does it regulate ESRE network genes through a 
      different mechanism?
  - question: 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?
suggested_experiments:
  - description: ChIP-seq to identify direct CEBP-2 binding sites genome-wide 
      and determine whether it binds CCAAT/enhancer elements and/or ESRE motifs.
  - description: 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.
tags:
  - caeel-surveillance-immunity

cebp-2

Gene Description

Existing Annotations Review

Core Functions

CEBP-2 forms heterodimers with other bZIP transcription factors including ZIP-2, ZIP-11, ATF-2, ATF-4, ATFS-1, CES-2, ZIP-3, and ZIP-9 via its leucine-zipper domain. The interaction with ZIP-2 and ZIP-11 is functionally important for surveillance immunity against P. aeruginosa.

References

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Deep Research Falcon

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Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

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Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

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