NSY-1 is the C. elegans ortholog of mammalian ASK1 (Apoptosis Signal-regulating Kinase 1), functioning as a MAP kinase kinase kinase (MAP3K) at the apex of a conserved p38 MAPK signaling cascade. NSY-1 phosphorylates and activates SEK-1 (MAPKK), which in turn activates PMK-1 (p38 MAPK). This pathway has two major biological roles: (1) Originally identified for its role in determining left/right asymmetric odorant receptor expression in AWC neurons (hence "neuronal symmetry" - nsy), where it acts downstream of calcium signaling via UNC-43/CaMKII and the TIR domain protein TIR-1 (SARM ortholog); (2) Critical for innate immunity, particularly defense against pathogenic bacteria (both Gram-positive and Gram-negative) and fungi. The protein localizes to post-synaptic regions of axons in neurons and is expressed in intestine, hypodermis, and neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: NSY-1 possesses protein kinase activity as demonstrated by direct biochemical assays. The IBA annotation is supported by phylogenetic inference across multiple orthologs including mammalian ASK1. Reason: This is a core molecular function of NSY-1. The protein kinase activity is well-established through biochemical studies (PMID:11336672, PMID:11751572). The IBA annotation from phylogenetic analysis is consistent with experimental evidence. Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and MAPK kinase kinase (MAPKKK), respectively PMID:11336672 nsy-1 encodes a homolog of the human MAP kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases file:worm/nsy-1/nsy-1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0007254 JNK cascade | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The IBA annotation indicates NSY-1 involvement in the JNK cascade based on phylogenetic inference. While there is some evidence for JNK pathway involvement in C. elegans stress responses involving nsy-1, the primary established role is in the p38 MAPK cascade. Reason: The mammalian ortholog ASK1 activates both p38 and JNK pathways. In C. elegans, there is evidence for JNK involvement in stress responses (PMID:15256590 shows JNK pathways defend against bacterial toxins), but the core established function of nsy-1 is in the p38 cascade via sek-1/pmk-1. The JNK cascade annotation is not wrong but represents a secondary function. Supporting Evidence: PMID:11336672 nsy-1 encodes a homolog of the human MAP kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases |
| GO:0038066 p38MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: NSY-1 is a core component of the p38 MAPK cascade in C. elegans, acting as the MAP3K that phosphorylates SEK-1 (MAPKK), which then activates PMK-1 (p38 MAPK). This is strongly supported by IBA phylogenetic inference and extensive experimental evidence. Reason: This is a core function of NSY-1. The nsy-1/sek-1/pmk-1 p38 MAPK cascade is one of the best-characterized signaling pathways in C. elegans innate immunity and neuronal development (PMID:12142542, PMID:11751572). Supporting Evidence: PMID:12142542 A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase |
| GO:0000165 MAPK cascade | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation based on InterPro domain mapping. NSY-1 contains a MAP3K domain and functions in the MAPK cascade. This is a parent term of the more specific p38MAPK cascade annotation. Reason: This broader term is correctly applied based on domain annotation. NSY-1 is indeed a MAP3K functioning in MAPK signaling. While more specific terms exist (p38MAPK cascade), this IEA annotation is not incorrect. Supporting Evidence: PMID:12142542 nsy-1, which encodes a MAP kinase kinase kinase |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: IEA annotation based on UniProt keyword mapping. As a kinase, NSY-1 binds ATP for its catalytic activity. This is a very general term. Reason: While technically correct (kinases bind nucleotides), this term is too general to be informative. The more specific term "ATP binding" (GO:0005524) is also annotated and is more appropriate for a kinase. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation based on InterPro domain mapping for protein kinase domain. This duplicates the IBA annotation with the same term but different evidence. Reason: Duplicate of IBA annotation - both are valid. The IEA provides independent support from domain analysis. Protein kinase activity is a core molecular function of NSY-1. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProt keyword mapping. NSY-1 is a serine/threonine kinase that phosphorylates SEK-1 on serine/threonine residues. Reason: This is an accurate more specific molecular function term. NSY-1 (ASK1 ortholog) is characterized as a serine/threonine kinase. The UniProt entry lists EC 2.7.11.25 (MAP kinase kinase kinase activity) which is a serine/threonine kinase. Supporting Evidence: UniProt:Q21029 Serine/threonine-protein kinase |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on EC number and automated reasoning. NSY-1 has MAP3K activity, phosphorylating SEK-1 (MAPKK). Reason: This is the most specific and accurate molecular function term for NSY-1. It is also supported by direct experimental evidence (IDA from PMID:11751572). This IEA provides additional computational support. Supporting Evidence: UniProt:Q21029 Mitogen-activated protein kinase kinase kinase nsy-1 |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on InterPro domain and UniProt keyword mapping. As a protein kinase, NSY-1 requires ATP binding for catalytic activity. Reason: ATP binding is essential for kinase activity. The protein contains a canonical ATP-binding site in its kinase domain. This is an appropriate molecular function annotation. |
| GO:0007399 nervous system development | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProt keyword "Neurogenesis". NSY-1 is involved in neuronal asymmetry determination during development. Reason: NSY-1 plays a well-established role in nervous system development, specifically in determining asymmetric odorant receptor expression in AWC neurons. This was the original context of nsy-1 discovery ("neuronal symmetry"). The term is appropriately broad. Supporting Evidence: PMID:11751572 the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII and establishes asymmetric cell fate decision during neuronal development |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Very general term from UniProt keyword mapping. NSY-1 has kinase activity, but more specific terms are available and annotated. Reason: This is technically correct but overly general. More specific terms (protein kinase activity, MAP kinase kinase kinase activity) are already annotated and provide more useful information. This general term adds no value. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Very general term from UniProt keyword mapping. Kinases are transferases, but this is at the root of the enzyme hierarchy. Reason: This is too general to be informative. While kinases are indeed transferases, this annotation provides no functional insight. More specific terms are already annotated. |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location vocabulary. NSY-1 localizes to axons in AWC neurons. Reason: NSY-1 localization to axons is experimentally demonstrated (PMID:15625192). The IEA annotation is consistent with experimental evidence. Supporting Evidence: PMID:15625192 TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location vocabulary. NSY-1 localizes to the neuronal cell body (perikaryon). Reason: NSY-1 localization to the perikaryon is supported by UniProt annotation based on experimental evidence (PMID:15625192). |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProt keyword mapping. NSY-1 requires Mg2+ as a cofactor for kinase activity. Reason: Kinases typically require divalent metal ions (Mg2+) as cofactors. The UniProt entry notes Mg2+ as a cofactor with experimental evidence (PMID:11751572). |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA annotation from Rhea reaction mapping. NSY-1 phosphorylates serine residues on substrate proteins. Reason: NSY-1 catalyzes serine phosphorylation as part of its MAP3K activity. This is consistent with the catalytic activity annotations in UniProt (EC 2.7.11.25). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba... | ACCEPT | Summary: IMP annotation showing nsy-1 positively regulates transcription of pgp-5 and other immune response genes. The p38 MAPK cascade activates transcription factors that drive gene expression. Reason: The nsy-1/sek-1/pmk-1 pathway regulates transcription of numerous genes including antimicrobial peptides and stress response genes. This is achieved through downstream transcription factors (PMID:17888400, PMID:17526726). Supporting Evidence: PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba... | ACCEPT | Summary: IMP annotation demonstrating nsy-1 is required for defense against Gram-negative bacteria including P. aeruginosa. Reason: This is a core biological process for nsy-1. The original identification of nsy-1 in innate immunity came from a screen for susceptibility to P. aeruginosa (Gram-negative) (PMID:12142542). Multiple studies confirm this role. Supporting Evidence: PMID:12142542 A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | IDA PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | MODIFY | Summary: IDA annotation based on direct assay of NSY-1 kinase activity in PMID:11751572. The study demonstrated NSY-1 phosphorylates SEK-1. Reason: While NSY-1 has protein kinase activity demonstrated by direct assay, it is specifically a serine/threonine kinase (EC 2.7.11.25), not a dual-specificity kinase. The term "protein serine/threonine/tyrosine kinase activity" implies tyrosine kinase activity which is not demonstrated. A more accurate term would be "MAP kinase kinase kinase activity" (GO:0004709) which is already annotated with IDA from the same reference. Proposed replacements: MAP kinase kinase kinase activity Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and MAPK kinase kinase (MAPKKK), respectively |
| GO:0006979 response to oxidative stress | IMP PMID:22308034 Stabilization of RNT-1 protein, runt-related transcription f... | ACCEPT | Summary: IMP annotation showing nsy-1 is required for the response to oxidative stress, specifically for stabilization of RNT-1 (RUNX transcription factor) during oxidative stress. Reason: NSY-1 plays a role in oxidative stress response through the p38 MAPK pathway. The study shows the MAP kinase pathway (including nsy-1) is required for RNT-1 stabilization in response to oxidative stress (PMID:22308034). Supporting Evidence: UniProt:Q21029 Plays a role in resistance to several environmental stresses including oxidative, protein misfolding (ER) and osmotic stresses PMID:22308034 Epub 2012 Feb 3. Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway. |
| GO:0140367 antibacterial innate immune response | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: IMP annotation based on the landmark study identifying nsy-1 as required for resistance to bacterial pathogens. Reason: This is a core function of nsy-1. The study (PMID:12142542) demonstrated that nsy-1 mutants are hypersusceptible to bacterial pathogens including P. aeruginosa and E. faecalis, establishing the p38 MAPK pathway in C. elegans innate immunity. Supporting Evidence: PMID:12142542 These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species |
| GO:0010628 positive regulation of gene expression | IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia... | ACCEPT | Summary: IMP annotation showing nsy-1 positively regulates expression of antimicrobial peptide genes in response to fungal infection. Reason: NSY-1 is part of the p38 MAPK cascade that positively regulates antimicrobial peptide gene expression. The study shows nsy-1 is required for nlp-29 induction after D. coniospora infection (PMID:22470487). Supporting Evidence: PMID:22470487 We have shown that for nlp-29 cluster genes, following both infection and injury, inductive signaling passes via TPA-1, a protein kinase C delta (PKC∂) that acts upstream of TIR-1, the nematode ortholog of SARM, and a MAPK cassette comprising the MAP3K NSY-1, the MAP2K SEK-1, and PMK-1 [20] |
| GO:0050832 defense response to fungus | IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia... | ACCEPT | Summary: IMP annotation demonstrating nsy-1 is required for defense against the fungal pathogen Drechmeria coniospora. Reason: NSY-1 is required for the innate immune response to fungal infection. The study identified nsy-1 mutants as unable to induce antimicrobial peptide expression after D. coniospora infection (PMID:22470487). Supporting Evidence: PMID:22470487 We undertook a large-scale genetic screen for mutants that prevented the normal induction of a Pnlp-29::GFP reporter transgene after infection with D. coniospora |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: IDA annotation based on direct biochemical demonstration that NSY-1 has MAP3K activity, phosphorylating SEK-1 (MAPKK). Reason: This is the most specific and accurate molecular function annotation for NSY-1. The study directly demonstrated NSY-1 kinase activity and its role as a MAP3K upstream of SEK-1 (PMID:11751572). Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and MAPK kinase kinase (MAPKKK), respectively |
| GO:0005737 cytoplasm | IDA PMID:15625192 A Toll-interleukin 1 repeat protein at the synapse specifies... | ACCEPT | Summary: IDA annotation showing NSY-1 localizes to the cytoplasm, based on fluorescence microscopy studies. Reason: NSY-1 localization to the cytoplasm is demonstrated in the Chuang & Bargmann study using NSY-1::GFP fusion proteins (PMID:15625192). Supporting Evidence: PMID:15625192 TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression |
| GO:0010628 positive regulation of gene expression | IMP PMID:17526726 Specificity and complexity of the Caenorhabditis elegans inn... | ACCEPT | Summary: IMP annotation showing nsy-1 positively regulates antimicrobial gene expression in response to bacterial pathogens. Reason: This is a core function of the nsy-1/p38 pathway. The study demonstrates differential regulation of antimicrobial genes by the p38 pathway including nsy-1 (PMID:17526726). Supporting Evidence: PMID:17526726 May 25. Specificity and complexity of the Caenorhabditis elegans innate immune response. |
| GO:1904115 axon cytoplasm | IDA PMID:15625192 A Toll-interleukin 1 repeat protein at the synapse specifies... | ACCEPT | Summary: IDA annotation showing NSY-1 localizes to the axon cytoplasm, specifically in post-synaptic punctate structures in AWC neurons. Reason: The study directly visualized NSY-1::GFP localization to punctate structures in AWC axons (PMID:15625192). This is a more specific term than "axon" and appropriately captures the localization data. Supporting Evidence: PMID:15625192 TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression |
| GO:0018991 egg-laying behavior | IMP PMID:10571181 Lateral signaling mediated by axon contact and calcium entry... | KEEP AS NON CORE | Summary: IMP annotation indicating nsy-1 affects egg-laying behavior based on mutant phenotypes. Reason: While nsy-1 mutants do show egg-laying defects, this is likely a pleiotropic effect of disrupted p38 MAPK signaling rather than a direct role in egg-laying behavior. The primary paper (PMID:10571181) focuses on neuronal asymmetry. The annotation is valid but represents a secondary phenotype. Supporting Evidence: UniProt:Q21029 Involved in egg laying PMID:10571181 Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. |
| GO:0008340 determination of adult lifespan | IMP PMID:23352664 A fasting-responsive signaling pathway that extends life spa... | KEEP AS NON CORE | Summary: IMP annotation based on the finding that nsy-1 is involved in fasting-responsive signaling that affects lifespan. Reason: The study (PMID:23352664) focuses on JNK (KGB-1) and AP-1 rather than nsy-1 as the primary mediators of fasting-induced longevity. NSY-1 may have a role through the broader MAPK signaling network, but this is not a core function. Supporting Evidence: PMID:23352664 Jan 24. A fasting-responsive signaling pathway that extends life span in C. |
| GO:0008340 determination of adult lifespan | IGI PMID:23352664 A fasting-responsive signaling pathway that extends life spa... | KEEP AS NON CORE | Summary: IGI annotation indicating genetic interaction affecting lifespan. Reason: As with the IMP annotation above, lifespan determination is not a core function of nsy-1. The genetic interaction evidence supports involvement but the primary pathway for fasting-induced longevity involves JNK/KGB-1 rather than the p38 pathway. Supporting Evidence: PMID:23352664 Jan 24. A fasting-responsive signaling pathway that extends life span in C. |
| GO:0042594 response to starvation | IMP PMID:23352664 A fasting-responsive signaling pathway that extends life spa... | KEEP AS NON CORE | Summary: IMP annotation indicating nsy-1 is involved in the response to starvation/fasting. Reason: While MAPK pathways are involved in stress responses including starvation, the study primarily implicates the JNK pathway (KGB-1) rather than the p38 pathway (nsy-1/sek-1/pmk-1) in fasting responses. This is not a core function. Supporting Evidence: PMID:23352664 Jan 24. A fasting-responsive signaling pathway that extends life span in C. |
| GO:0042594 response to starvation | IGI PMID:23352664 A fasting-responsive signaling pathway that extends life spa... | KEEP AS NON CORE | Summary: IGI annotation for genetic interaction in starvation response. Reason: Same reasoning as IMP annotation above - not a core function of nsy-1. Supporting Evidence: PMID:23352664 Jan 24. A fasting-responsive signaling pathway that extends life span in C. |
| GO:0093002 response to nematicide | TAS PMID:15256590 Mitogen-activated protein kinase pathways defend against bac... | ACCEPT | Summary: TAS annotation indicating nsy-1 is involved in defense against bacterial pore-forming toxins, which can act as nematicides. Reason: The study (PMID:15256590) demonstrates that p38 MAPK pathways including nsy-1 defend against the pore-forming toxin Cry5B from Bacillus thuringiensis, a natural nematicide. This is a valid biological process annotation. Supporting Evidence: PMID:15256590 A p38 mitogen-activated protein kinase (MAPK) kinase and a c-Jun N-terminal-like MAPK are both transcriptionally up-regulated by Cry5B |
| GO:0000165 MAPK cascade | IGI PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: IGI annotation based on genetic interaction with sek-1 (WBGene00004758) in the MAPK cascade for neuronal asymmetry. Reason: NSY-1 functions in the MAPK cascade upstream of SEK-1. The genetic interaction evidence demonstrates the pathway relationship (PMID:11751572). Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1 |
| GO:0031434 mitogen-activated protein kinase kinase binding | IPI PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: IPI annotation based on physical interaction between NSY-1 and SEK-1 (MAPKK). Reason: NSY-1 physically interacts with SEK-1 as part of the MAPK signaling complex. This interaction is required for signal transduction (PMID:11751572). Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1 UniProt:Q21029 Interacts with sek-1 |
| GO:0035545 determination of left/right asymmetry in nervous system | IMP PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: IMP annotation based on the finding that nsy-1 mutants disrupt left/right asymmetric odorant receptor expression in AWC neurons. Reason: This is a core biological function of nsy-1 and the origin of its name ("neuronal symmetry"). The gene was identified in screens for mutants with symmetric str-2 expression in both AWC neurons (PMID:11751572). Supporting Evidence: PMID:11751572 the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII and establishes asymmetric cell fate decision during neuronal development PMID:11336672 nsy-1 mutants express str-2 in both neurons, disrupting AWC asymmetry |
| GO:0035545 determination of left/right asymmetry in nervous system | IGI PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: IGI annotation based on genetic interaction with sek-1 in determination of neuronal asymmetry. Reason: The genetic interaction between nsy-1 and sek-1 in the asymmetry pathway is well-established (PMID:11751572). Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1 |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: IMP annotation showing nsy-1 is required for defense against Gram-positive bacteria (E. faecalis tested). Reason: This is a core function of nsy-1. The landmark study (PMID:12142542) demonstrated nsy-1 mutants are susceptible to both Gram-positive (E. faecalis) and Gram-negative (P. aeruginosa) pathogens. Supporting Evidence: UniProt:Q21029 Involved in resistance to pathogenic Gram-positive and Gram-negative bacterial and fungal infection PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: IMP annotation showing nsy-1 is required for defense against Gram-negative bacteria (P. aeruginosa). Reason: Core function - nsy-1 was identified in a screen for susceptibility to P. aeruginosa (PMID:12142542). This duplicates another annotation with the same term from PMID:17888400. Supporting Evidence: PMID:12142542 A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance |
| GO:0038066 p38MAPK cascade | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: IMP annotation demonstrating nsy-1 functions in the p38 MAPK cascade for innate immunity. Reason: Core function - the study established that nsy-1/sek-1/pmk-1 constitute a conserved p38 MAPK cascade for innate immunity (PMID:12142542). Supporting Evidence: PMID:12142542 RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense |
| GO:1901046 positive regulation of egg-laying behavior | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | KEEP AS NON CORE | Summary: IMP annotation indicating nsy-1 positively regulates egg-laying behavior. Reason: While nsy-1 mutants show egg-laying defects, this is likely a secondary phenotype of disrupted MAPK signaling rather than a primary function. The reference (PMID:12142542) focuses on innate immunity, not egg-laying. Supporting Evidence: UniProt:Q21029 Involved in egg laying PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. |
| GO:0014069 postsynaptic density | IDA PMID:15625192 A Toll-interleukin 1 repeat protein at the synapse specifies... | ACCEPT | Summary: IDA annotation showing NSY-1 localizes to postsynaptic density in AWC neurons. Reason: NSY-1 localizes to postsynaptic regions where it co-localizes with TIR-1 (PMID:15625192). This localization is important for its role in neuronal asymmetry signaling. Supporting Evidence: PMID:15625192 TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression |
| GO:0043025 neuronal cell body | IDA PMID:15625192 A Toll-interleukin 1 repeat protein at the synapse specifies... | ACCEPT | Summary: IDA annotation showing NSY-1 localizes to neuronal cell bodies (perikaryon). Reason: NSY-1::GFP localization studies showed expression in neuronal cell bodies in addition to axons (PMID:15625192). Supporting Evidence: PMID:15625192 A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. |
| GO:0006935 chemotaxis | IMP PMID:11287957 C. elegans odour discrimination requires asymmetric diversit... | ACCEPT | Summary: IMP annotation showing nsy-1 affects chemotaxis behavior, specifically odor discrimination. Reason: nsy-1 mutants show defects in odor discrimination and chemotaxis due to disrupted AWC asymmetry. The study shows "nsy-1 mutants exhibit discrimination and olfactory defects" (PMID:11287957). Supporting Evidence: PMID:11287957 C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. |
| GO:0045087 innate immune response | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: IMP annotation showing nsy-1 is required for innate immune response. Reason: This is a core function of nsy-1. The gene was identified in a screen for innate immunity mutants and is required for defense against pathogens (PMID:12142542). Supporting Evidence: PMID:12142542 These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species |
| GO:0045165 cell fate commitment | IMP PMID:10571181 Lateral signaling mediated by axon contact and calcium entry... | ACCEPT | Summary: IMP annotation indicating nsy-1 is involved in cell fate commitment, specifically in AWC neuronal asymmetry. Reason: NSY-1 is required for the commitment of AWC neurons to asymmetric fates (AWC-ON vs AWC-OFF). The pathway determines which neuron expresses str-2 (PMID:10571181, PMID:11751572). Supporting Evidence: PMID:11751572 the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII and establishes asymmetric cell fate decision during neuronal development PMID:10571181 Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. |
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