irg-1 (infection response gene 1) is a key marker gene of the C. elegans innate immune response that is strongly and specifically induced upon infection with virulent Pseudomonas aeruginosa strain PA14. The gene is expressed in the intestine and is regulated by the bZIP transcription factor zip-2, which is activated in response to pathogen-induced translational inhibition (particularly via P. aeruginosa exotoxin A). irg-1 is induced independently of several classical immunity pathways including pmk-1/p38 MAPK, dbl-1/TGF-beta, kgb-1/JNK, and bar-1/beta-catenin. The protein contains a NADAR (NAD- and ADP-ribose-associated) domain, suggesting potential enzymatic activity related to ADP-ribose metabolism, though direct antimicrobial function has not been experimentally demonstrated. irg-1::GFP reporters are widely used as readouts for immune activation in C. elegans studies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: This IEA annotation is based on UniProtKB keyword mapping (KW-0391 Immunity). While irg-1 is clearly involved in immunity based on its strong induction during P. aeruginosa infection (PMID:20133860), this term is quite broad. More specific child terms are already annotated. Reason: Although this is a broad parent term, it is appropriate as a high-level classification for irg-1. The gene is named "infection response gene 1" and is characterized as being induced during immune responses. While more specific terms like GO:0045087 (innate immune response) and GO:0140367 (antibacterial innate immune response) are also present and more informative, retaining the parent term does not cause harm and provides a general classification that correctly captures irg-1's involvement in immunity. Supporting Evidence: PMID:20133860 We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. file:worm/irg-1/irg-1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: This IEA annotation is based on UniProtKB keyword mapping (KW-0399 Innate immunity). irg-1 is definitively involved in innate immune responses as demonstrated by its specific induction during P. aeruginosa infection and its regulation by zip-2 (PMID:20133860). Reason: This term accurately reflects irg-1's role. C. elegans lacks adaptive immunity, so all immune responses are innate. irg-1 expression is strongly induced during pathogen infection and the protein is part of the zip-2-mediated early innate immune response pathway. This IEA annotation is well-supported by the literature. Supporting Evidence: PMID:20133860 These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: The ND (No Data) annotation indicates that no molecular function has been experimentally characterized for irg-1. Interestingly, irg-1 contains a NADAR domain (IPR012816), which in other proteins is associated with ADP-ribosylhydrolase activity, particularly the ability to remove ADP-ribose from guanine bases. However, no enzymatic activity has been demonstrated for irg-1 itself. Reason: This ND annotation is appropriate as no molecular function has been experimentally validated for irg-1. While the NADAR domain suggests potential hydrolase activity, this remains uncharacterized. The protein may function as an effector in antimicrobial defense but specific molecular activity awaits experimental confirmation. The ND annotation correctly reflects our current state of knowledge. |
| GO:0140367 antibacterial innate immune response | IEP PMID:20133860 bZIP transcription factor zip-2 mediates an early response t... | ACCEPT | Summary: This IEP (Inferred from Expression Pattern) annotation indicates irg-1 is involved in antibacterial innate immune response based on its strong upregulation during P. aeruginosa infection. The original paper (PMID:20133860) showed that irg-1 is specifically induced by virulent P. aeruginosa but not by attenuated mutants or other pathogens. Reason: This annotation accurately reflects the published evidence. irg-1 expression is induced specifically by pathogenic bacteria (P. aeruginosa PA14) and the zip-2 pathway that regulates irg-1 is important for defense against bacterial infection. The IEP evidence code is appropriate since the annotation is based on expression pattern during bacterial infection rather than direct functional characterization of the protein. Supporting Evidence: PMID:20133860 We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. PMID:20133860 This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. |
| GO:0050829 defense response to Gram-negative bacterium | IEP PMID:20133860 bZIP transcription factor zip-2 mediates an early response t... | ACCEPT | Summary: This annotation captures irg-1's role in defense specifically against Gram-negative bacteria, based on its induction by P. aeruginosa (a Gram-negative pathogen). The annotation is based on expression pattern data from PMID:20133860. Reason: This is an appropriate and specific annotation. P. aeruginosa is a Gram-negative bacterium and irg-1 is specifically induced during infection with this pathogen. The term correctly specifies the type of pathogen against which irg-1-mediated defense operates. The IEP evidence code is suitable given that the evidence comes from expression studies during bacterial infection. Supporting Evidence: PMID:20133860 We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: The ND annotation indicates no specific cellular component localization has been determined for irg-1. While the protein is known to be expressed in intestinal cells (PMID:20133860), the subcellular localization within those cells has not been characterized. Reason: This ND annotation is appropriate. Although irg-1 is expressed in the intestine at the tissue level, no subcellular localization data exists for the protein. The UniProt entry notes "Expressed in the intestine" but this refers to tissue specificity rather than cellular component. The ND annotation correctly reflects the lack of subcellular localization data. |
| GO:0045087 innate immune response | HEP PMID:16968778 A conserved role for a GATA transcription factor in regulati... | ACCEPT | Summary: This HEP (High Throughput Expression Pattern) annotation from PMID:16968778 (Shapira et al.) is based on genome-wide transcriptomic analysis showing genes induced during P. aeruginosa infection. This study identified ELT-2 as a major regulator of intestinal protective responses to infection. Reason: This annotation is valid and provides independent support from a different study. The Shapira et al. paper performed genome-wide transcriptomic analysis identifying genes induced during P. aeruginosa infection, which would include irg-1 as an infection-responsive gene. The HEP evidence code is appropriate for high-throughput expression data. Note that this annotation uses a different evidence code (HEP) than the IEA annotation for the same term, reflecting different sources of evidence, which is appropriate. Supporting Evidence: PMID:16968778 Gene expression and functional RNAi-based analyses identified the tissue-specific GATA transcription factor ELT-2 as a major regulator of an early intestinal protective response to infection with the human bacterial pathogen Pseudomonas aeruginosa. |
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Download this section (compressed HTML)Q: Does irg-1 possess ADP-ribosylhydrolase activity given its NADAR domain (IPR012816)?
Q: Does irg-1 have direct antimicrobial activity or does it serve primarily as a marker of immune pathway activation?
Q: What is the subcellular localization of irg-1 protein within intestinal cells?
Experiment: Purify recombinant irg-1 and test for ability to remove ADP-ribose from guanine-conjugated substrates, given the presence of the NADAR domain. This would determine whether irg-1 has enzymatic function or is a pseudoenzyme.
Hypothesis: irg-1 possesses ADP-ribosylhydrolase activity based on its NADAR domain
Experiment: Test whether purified irg-1 protein has direct antimicrobial activity against bacteria, particularly P. aeruginosa, using in vitro killing assays.
Hypothesis: irg-1 functions as a direct antimicrobial effector molecule
Experiment: Generate irg-1 knockout or knockdown strains and test survival on P. aeruginosa to determine whether irg-1 itself is required for defense or is just a marker of pathway activation.
Hypothesis: irg-1 is functionally required for defense against P. aeruginosa infection
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