Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000165 MAPK cascade	IBA GO_REF:0000033	ACCEPT	Summary: SEK-1 is definitively part of the p38 MAPK cascade, functioning between NSY-1 (MAPKKK) and PMK-1 (p38 MAPK). This has been demonstrated in multiple studies showing the signaling hierarchy (PMID:11751572, PMID:12142542). The phylogenetic inference from PAINT is consistent with experimental data. Reason: Core function well-established by multiple experimental studies. SEK-1 is the direct MAPKK in the conserved p38 cascade. 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 PMID:11751572 the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII file:worm/sek-1/sek-1-deep-research-falcon.md model: Edison Scientific Literature
GO:0004708 MAP kinase kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: SEK-1 has demonstrated MAP kinase kinase activity, phosphorylating PMK-1/p38 on both serine/threonine and tyrosine residues (PMID:11751572). The IBA annotation accurately reflects this core molecular function. Reason: Core molecular function supported by direct biochemical evidence. SEK-1 phosphorylates and activates PMK-1 (p38 MAPK). Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development
GO:0000165 MAPK cascade	IEA GO_REF:0000117	ACCEPT	Summary: This IEA annotation from ARBA machine learning correctly identifies SEK-1's role in the MAPK cascade. It is consistent with the more specific IBA annotation and extensive experimental evidence. Reason: Accurate automated annotation consistent with experimental evidence.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: As a kinase, SEK-1 requires nucleotide binding for catalytic activity. However, this is a very general term; ATP binding (GO:0005524) would be more informative. Reason: Accurate but very general annotation for a kinase. The more specific ATP binding annotation is also present.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: SEK-1 has protein kinase activity as demonstrated by its ability to phosphorylate PMK-1. However, this is a broad term; more specific terms like MAP kinase kinase activity are more informative. Reason: Accurate parent term for the more specific MAP kinase kinase activity.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000043	ACCEPT	Summary: SEK-1 phosphorylates PMK-1 on serine and threonine residues as part of its dual-specificity kinase activity. This annotation is accurate. Reason: Component of the dual-specificity kinase activity demonstrated for SEK-1.
GO:0004708 MAP kinase kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC-based annotation correctly identifies SEK-1's MAP kinase kinase activity (EC 2.7.12.2). This is consistent with experimental evidence. Reason: Accurate annotation based on enzyme classification, supported by experimental data.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: SEK-1 is a dual-specificity kinase that phosphorylates tyrosine in addition to serine/threonine. This annotation is accurate for a MAPKK. Reason: Component of dual-specificity kinase activity characteristic of MAPKKs.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: Kinases require ATP as a phosphate donor. The UniProt record indicates ATP binding at residues 56-64 and K79. Reason: Essential for kinase activity; supported by sequence analysis.
GO:0007399 nervous system development	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: SEK-1 is involved in AWC neuronal asymmetric development (PMID:11751572). This general term is accurate but non-specific. Reason: While accurate, the more specific term 'determination of left/right asymmetry in nervous system' (GO:0035545) better captures SEK-1's role.
GO:0016301 kinase activity	IEA GO_REF:0000043	ACCEPT	Summary: Very broad parent term; more specific kinase activity terms are present. Reason: Accurate parent term in the kinase hierarchy.
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: Very broad parent term for kinase activity. Reason: Accurate but very general parent term.
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: Kinases typically require Mg2+ as a cofactor for ATP hydrolysis. This is a standard requirement for protein kinases. Reason: Accurate; metal ion binding (Mg2+) is required as cofactor for kinase activity.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: SEK-1 phosphorylates serine residues on its substrates. This is part of its dual-specificity kinase function. Reason: Component of dual-specificity kinase activity.
GO:0000165 MAPK cascade	IGI PMID:22308034 Stabilization of RNT-1 protein, runt-related transcription f...	ACCEPT	Summary: This study demonstrates SEK-1's role in the MAPK cascade in the context of oxidative stress response and RNT-1 stabilization. The IGI evidence with PMK-1 (Q17446) is appropriate. Reason: Well-supported by genetic interaction data in oxidative stress context. Supporting Evidence: PMID:22308034 The MAP kinase pathway is required for RNT-1 stabilization, and RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro
GO:0000165 MAPK cascade	IMP PMID:20008556 The Caenorhabditis elegans Ste20-related kinase and Rac-type...	ACCEPT	Summary: This study examined MAPK pathways in stress response. While the paper primarily focuses on the JNK pathway (MLK-1-MEK-1-KGB-1), it provides context for MAPK signaling that includes the p38 pathway. Reason: IMP evidence for MAPK cascade involvement, though the paper emphasizes JNK pathway. Supporting Evidence: PMID:20008556 Dec 14. The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the stress response.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba...	KEEP AS NON CORE	Summary: This study shows that SEK-1 is required for pgp-5 transcriptional induction in response to bacterial infection, which requires TIR-1 and the p38 MAPK cascade. Reason: This is a downstream consequence of SEK-1's role in the p38 cascade rather than a core function. The transcriptional activation is mediated by downstream transcription factors like SKN-1. Supporting Evidence: PMID:17888400 pgp-5 is induced by both bacterial infection and heavy metal stress
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba...	ACCEPT	Summary: SEK-1 is required for resistance to Pseudomonas aeruginosa infection. The p38 MAPK pathway (including SEK-1) mediates innate immune responses against Gram-negative bacteria. Reason: Core function of SEK-1 in innate immunity is well-established. Multiple studies confirm this role (PMID:12142542, PMID:17888400, PMID:19454349). 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 PMID:17888400 signals from both biotic and abiotic stresses are integrated by TIR-1... and a p38 MAP kinase signaling cassette
GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reti...	KEEP AS NON CORE	Summary: This study demonstrates that SEK-1/PMK-1 signaling protects against ER stress and dopaminergic neuron degeneration in the context of LRRK2 signaling. The sek-1 mutant shows enhanced sensitivity to 6-OHDA-induced neurotoxicity. Reason: This represents a specific context (dopaminergic neuron protection, LRRK2 pathway) rather than a core function of SEK-1. The term is quite specific to this study. Supporting Evidence: PMID:21857923 nematodes with a loss-of-function mutation in sek-1 consistently displayed enhanced susceptibility to 6-OHDA-induced neurotoxicity
GO:0004712 protein serine/threonine/tyrosine kinase activity	IDA PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as...	ACCEPT	Summary: This is direct biochemical evidence for SEK-1's dual-specificity kinase activity. The paper demonstrates that SEK-1 phosphorylates PMK-1 on both Ser/Thr and Tyr residues. Reason: Core molecular function with direct experimental evidence. This accurately describes SEK-1 as a dual-specificity MAPKK. Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development
GO:0006979 response to oxidative stress	IMP PMID:22308034 Stabilization of RNT-1 protein, runt-related transcription f...	ACCEPT	Summary: SEK-1 is required for stabilization of RNT-1 during oxidative stress and for the oxidative stress response mediated through PMK-1 and SKN-1. Reason: Important function of the p38 cascade in C. elegans oxidative stress response. Supporting Evidence: PMID:22308034 RNT-1 was rapidly stabilized by oxidative stress... The MAP kinase pathway is required for RNT-1 stabilization PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response
GO:0106310 protein serine kinase activity	IGI PMID:22308034 Stabilization of RNT-1 protein, runt-related transcription f...	ACCEPT	Summary: Genetic interaction with PMK-1 supports SEK-1's serine kinase activity in the context of RNT-1 phosphorylation during oxidative stress. Reason: Supports the biochemical evidence for SEK-1 kinase activity. Supporting Evidence: PMID:22308034 RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro
GO:0140367 antibacterial innate immune response	IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans...	ACCEPT	Summary: This seminal paper established SEK-1's role in innate immunity against bacterial pathogens. sek-1 mutants show enhanced susceptibility to killing by P. aeruginosa and other pathogens. Reason: Core function of SEK-1 in innate immunity, established in the foundational paper for this pathway. 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
GO:0010628 positive regulation of gene expression	IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia...	KEEP AS NON CORE	Summary: SEK-1 is required for induction of antimicrobial peptide gene expression (nlp-29 cluster) following fungal infection. This is a downstream effect of the p38 cascade. Reason: This is a downstream consequence of SEK-1's signaling role rather than a core function. The annotation to immune response is more informative. Supporting Evidence: PMID:22470487 inductive signaling passes via TPA-1... and a MAPK cassette comprising the MAP3K NSY-1, the MAP2K SEK-1, and PMK-1
GO:0050832 defense response to fungus	IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia...	ACCEPT	Summary: SEK-1 is required for antimicrobial peptide gene induction following infection with the fungus Drechmeria coniospora. This expands the innate immune function beyond bacteria. Reason: Important extension of SEK-1's innate immune function to fungal pathogens. Supporting Evidence: PMID:22470487 inductive signaling passes via TPA-1... and a MAPK cassette comprising the MAP3K NSY-1, the MAP2K SEK-1, and PMK-1... We have shown that for nlp-29 cluster genes, following both infection and injury
GO:0004708 MAP kinase kinase activity	IDA PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as...	ACCEPT	Summary: Direct biochemical demonstration of SEK-1's MAPKK activity, showing it phosphorylates and activates PMK-1. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resista...	ACCEPT	Summary: This study on mitochondrial UPR shows that pre-activation of UPR enhances survival of sek-1 mutants exposed to P. aeruginosa, confirming SEK-1's role in defense against Gram-negative bacteria. Reason: Additional evidence supporting SEK-1's role in defense against Gram-negative pathogens. Supporting Evidence: PMID:25274306 pre-activation of the UPRmt enhanced the survival of the pmk-1 and sek-1 mutants
GO:0050829 defense response to Gram-negative bacterium	IGI PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resista...	ACCEPT	Summary: Genetic interaction with ATFS-1 in the context of P. aeruginosa defense supports SEK-1's role in innate immunity. Reason: Genetic interaction data supporting SEK-1's immune function. Supporting Evidence: PMID:25274306 pre-activation of the UPRmt enhanced the survival of the pmk-1 and sek-1 mutants
GO:0050830 defense response to Gram-positive bacterium	IMP PMID:24972867 Orthosiphon stamineus protects Caenorhabditis elegans agains...	ACCEPT	Summary: This study shows SEK-1 is required for protection against Staphylococcus aureus infection. The p38 MAP kinase pathway mediates the protective effect. Reason: Extends SEK-1's innate immune function to Gram-positive pathogens. Supporting Evidence: PMID:24972867 The effect of UE-12 is diminished in sek-1 (km4) and pmk-1 (km25) mutants... the p38 MAP kinase and insulin-like signaling pathways
GO:0009636 response to toxic substance	IMP PMID:21408619 Global functional analyses of cellular responses to pore-for...	KEEP AS NON CORE	Summary: This study on cellular responses to pore-forming toxins shows that the p38 MAPK pathway (including SEK-1) is important for defense against bacterial toxins. Reason: Related to innate immunity function but very general. More specific defense response annotations are present. Supporting Evidence: PMID:21408619 the p38 mitogen-activated protein kinase (MAPK) pathway was the first intracellular pathway demonstrated to protect cells against PFTs
GO:0093002 response to nematicide	IMP PMID:15256590 Mitogen-activated protein kinase pathways defend against bac...	ACCEPT	Summary: SEK-1 is required for defense against bacterial pore-forming toxins like Cry5B from Bacillus thuringiensis. sek-1 is transcriptionally upregulated by Cry5B and mutants are hypersensitive to the toxin. Reason: Important function in response to natural nematode pathogens/toxins. 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: Genetic interactions with nsy-1 (MAPKKK) and pmk-1 (MAPK) establish SEK-1's position in the MAPK cascade. Reason: Foundational genetic evidence for SEK-1's role in the p38 cascade. Supporting Evidence: PMID:11751572 the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII
GO:0031435 mitogen-activated protein kinase kinase kinase binding	IPI PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as...	ACCEPT	Summary: SEK-1 physically interacts with NSY-1 (MAPKKK). This interaction is essential for pathway function. Reason: Direct protein interaction evidence for SEK-1-NSY-1 binding. Supporting Evidence: PMID:11751572 SEK-1 functions in a pathway downstream of UNC-43 and NSY-1
GO:0034607 turning behavior involved in mating	IMP PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as...	KEEP AS NON CORE	Summary: sek-1 mutants show defects in male mating behavior, likely related to neuronal signaling functions. Reason: This is likely a pleiotropic effect of the neuronal asymmetry function rather than a core function. Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans.
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: SEK-1 is essential for establishing asymmetric cell fates in the AWC olfactory neurons. This is one of the two major biological roles of SEK-1. Reason: Core function of SEK-1 in neuronal development, established in the foundational paper. Supporting Evidence: PMID:11751572 SEK-1 is required for asymmetric expression in AWC neurons... the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling through CaMKII and establishes asymmetric cell fate decision during neuronal development
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: Genetic interaction with nsy-1 in the context of AWC asymmetry supports this annotation. Reason: Genetic evidence supporting the neuronal asymmetry function. Supporting Evidence: PMID:11751572 Genetic and biochemical analyses reveal that SEK-1 functions in a pathway downstream of UNC-43 and NSY-1
GO:0046662 regulation of egg-laying behavior	IMP PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as...	KEEP AS NON CORE	Summary: sek-1 mutants show egg-laying defects. The UniProt record notes "Egg-laying defect" for the G212R mutant. Reason: This is likely a pleiotropic effect rather than a core function. Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans.
GO:0050830 defense response to Gram-positive bacterium	IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans...	ACCEPT	Summary: The foundational paper showed sek-1 mutants have enhanced susceptibility to Enterococcus faecalis (Gram-positive). Reason: Core innate immunity function established in the foundational paper. 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
GO:0038066 p38MAPK cascade	IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans...	ACCEPT	Summary: This is the most specific term for SEK-1's role in the MAPK cascade. The paper establishes SEK-1 as a component of the conserved p38 MAPK pathway. Reason: Most appropriate specific term for SEK-1's signaling function. Supporting Evidence: PMID:12142542 RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans...	ACCEPT	Summary: sek-1 was identified in a screen for mutants with enhanced susceptibility to P. aeruginosa (Gram-negative). Reason: Core innate immunity function from the foundational study. 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
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: sek-1 mutants show reduced egg-laying. This annotation is more specific than 'regulation of egg-laying behavior'. Reason: Pleiotropic effect; not a core function of SEK-1. Supporting Evidence: PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity.
GO:0000302 response to reactive oxygen species	IMP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati...	ACCEPT	Summary: SEK-1/PMK-1 pathway regulates SKN-1 nuclear localization during oxidative stress. gcs-1 expression in response to arsenite requires this pathway. Reason: Important stress response function linked to core p38 signaling. Supporting Evidence: PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response
GO:0000303 response to superoxide	IMP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati...	ACCEPT	Summary: More specific child term of response to ROS. The p38 pathway responds to oxidative stress including superoxide. Reason: Specific oxidative stress response function. Supporting Evidence: PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1
GO:0045087 innate immune response	IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente...	ACCEPT	Summary: SEK-1 is required for conditioning-mediated protection against enteropathogenic E. coli. The p38 MAPK pathway mediates this innate immune response. Reason: Core innate immunity function. Supporting Evidence: PMID:19454349 Conditioning requires dopaminergic neurons; the p38 MAP kinase pathway, which regulates innate immunity
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente...	ACCEPT	Summary: Protection against enteropathogenic E. coli requires SEK-1/PMK-1 signaling. Reason: Additional evidence for innate immune function against Gram-negative bacteria. Supporting Evidence: PMID:19454349 Conditioning requires... the p38 MAP kinase pathway, which regulates innate immunity
GO:0045087 innate immune response	IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans...	ACCEPT	Summary: Foundational evidence for SEK-1's role in innate immunity. sek-1 mutants show enhanced susceptibility to multiple pathogens. Reason: Core function established in the seminal paper. Supporting Evidence: PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity

Core Functions

Direct biochemical evidence (IDA, PMID:11751572) demonstrates SEK-1 phosphorylates and activates PMK-1 (p38 MAPK). SEK-1 is a dual-specificity kinase phosphorylating both serine/threonine and tyrosine residues.

Molecular Function:

MAP kinase kinase activity

Directly Involved In:

p38MAPK cascade

sek-1 mutants show enhanced susceptibility to multiple bacterial pathogens including P. aeruginosa, E. faecalis, and S. aureus (PMID:12142542, PMID:24972867).

Molecular Function:

MAP kinase kinase activity

Directly Involved In:

antibacterial innate immune response

SEK-1 is required for asymmetric cell fate determination in AWC olfactory neurons, acting downstream of calcium/CaMKII signaling (PMID:11751572).

Molecular Function:

MAP kinase kinase activity

Directly Involved In:

determination of left/right asymmetry in nervous system

SEK-1/PMK-1 pathway regulates SKN-1 nuclear localization and RNT-1 stabilization during oxidative stress (PMID:16166371, PMID:22308034).

Molecular Function:

MAP kinase kinase activity

Directly Involved In:

response to oxidative stress

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

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

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11751572

SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans.

SEK-1 is required for asymmetric expression of str-2 in AWC neurons

"SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans."
SEK-1 functions downstream of UNC-43 (CaMKII) and NSY-1 (MAPKKK)

"SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans."
SEK-1 interacts with NSY-1

"SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans."
Demonstrates dual-specificity kinase activity

"SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans."
Activated by phosphorylation at Ser-204 and Thr-208

"SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans."

PMID:12142542

A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity.

sek-1 identified in screen for enhanced susceptibility to P. aeruginosa

"A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity."
nsy-1/sek-1/pmk-1 form conserved p38 MAPK pathway for pathogen defense

"A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity."
sek-1 mutants hypersensitive to bacterial pathogens

"A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity."

PMID:15256590

Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins.

p38 MAPK pathway required for defense against Cry5B toxin

"Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins."
sek-1 transcriptionally upregulated by Cry5B

"Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins."

PMID:16166371

The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response.

p38 pathway regulates SKN-1 nuclear localization during oxidative stress

"The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response."
gcs-1 expression requires p38 pathway

"The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response."

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.

pgp-5 induction requires TIR-1 and p38 cascade including SEK-1

"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."

PMID:19454349

Conditioning protects C. elegans from lethal effects of enteropathogenic E. coli by activating genes that regulate lifespan and innate immunity.

Conditioning protection requires p38 MAP kinase pathway

"Conditioning protects C. elegans from lethal effects of enteropathogenic E. coli by activating genes that regulate lifespan and innate immunity."

PMID:20008556

The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the stress response.

Context for MAPK signaling in stress response

"The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the stress response."

PMID:21408619

Global functional analyses of cellular responses to pore-forming toxins.

p38 MAPK pathway important for defense against pore-forming toxins

"Global functional analyses of cellular responses to pore-forming toxins."

PMID:21857923

Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans.

sek-1 mutants show enhanced sensitivity to 6-OHDA neurotoxicity

"Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."
sek-1 functions in same pathway as lrk-1 and pmk-1

"Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."

PMID:22308034

Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway.

RNT-1 phosphorylated by SEK-1/PMK-1 in vitro

"Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway."
MAP kinase pathway required for RNT-1 stabilization during oxidative stress

"Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway."

PMID:22470487

The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene expression.

SEK-1 part of MAPK cassette for nlp-29 induction

"The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene expression."
Required for antimicrobial peptide expression after fungal infection

"The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene expression."

PMID:24972867

Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation.

SEK-1 required for p38 MAPK-mediated protection against S. aureus

"Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation."

PMID:25274306

Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection.

UPRmt pre-activation enhances survival of sek-1 mutants during P. aeruginosa infection

"Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection."
UPRmt can function independently of NSY-1/SEK-1/PMK-1 pathway

"Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection."

file:worm/sek-1/sek-1-deep-research-falcon.md

Deep research report on sek-1

📚 Additional Documentation

Deep Research Falcon

(sek-1-deep-research-falcon.md)

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gene_id: sek-1
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gene_info: Name=sek-1 {ECO:0000312|WormBase:R03G5.2}; ORFNames=R03G5.2 {ECO:0000312|WormBase:R03G5.2};
organism_full: Caenorhabditis elegans.
protein_family: Belongs to the protein kinase superfamily. STE Ser/Thr
protein_domains: Kinase-like_dom_sf. (IPR011009); Prot_kinase_dom. (IPR000719);
Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271); Pkinase (PF00069)
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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: G5EDF7
Protein Description: RecName: Full=Dual specificity mitogen-activated protein kinase kinase sek-1 {ECO:0000305|PubMed:11751572}; Short=MAP kinase kinase sek-1 {ECO:0000305}; EC=2.7.12.2 {ECO:0000269|PubMed:11751572};
Gene Information: Name=sek-1 {ECO:0000312|WormBase:R03G5.2}; ORFNames=R03G5.2 {ECO:0000312|WormBase:R03G5.2};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the protein kinase superfamily. STE Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); Prot_kinase_dom. (IPR000719); Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271); Pkinase (PF00069)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "sek-1" 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 'sek-1' 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 sek-1 (gene ID: sek-1, UniProt: G5EDF7) 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: G5EDF7
Protein Description: RecName: Full=Dual specificity mitogen-activated protein kinase kinase sek-1 {ECO:0000305|PubMed:11751572}; Short=MAP kinase kinase sek-1 {ECO:0000305}; EC=2.7.12.2 {ECO:0000269|PubMed:11751572};
Gene Information: Name=sek-1 {ECO:0000312|WormBase:R03G5.2}; ORFNames=R03G5.2 {ECO:0000312|WormBase:R03G5.2};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the protein kinase superfamily. STE Ser/Thr
Key Domains: Kinase-like_dom_sf. (IPR011009); Prot_kinase_dom. (IPR000719); Protein_kinase_ATP_BS. (IPR017441); Ser/Thr_kinase_AS. (IPR008271); Pkinase (PF00069)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "sek-1" 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 sek-1 (gene ID: sek-1, UniProt: G5EDF7) 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.

Research plan and verification
We verified the target identity before proceeding. See the mandatory identity check below.

sek-1 (UniProt G5EDF7) in Caenorhabditis elegans is the MAPKK (dual-specificity MAP kinase kinase) functioning in the canonical NSY-1 → SEK-1 → PMK-1/PMK-2 p38 MAPK cascade. (hoyt2017thesek1p38 pages 1-2, sakaguchi2004rolesofmap pages 3-4)
SEK-1 belongs to the STE Ser/Thr protein kinase family and contains conserved Pkinase (PF00069) and kinase-like (IPR011009) domains consistent with MAPKK enzymatic function. (sakaguchi2004rolesofmap pages 3-4)
Note: mammalian MKK3/6 are homologous MAPKKs but are distinct orthologs; ensure literature pertains to C. elegans SEK-1 (UniProt G5EDF7) to avoid cross-species symbol confusion. (andrusiak2016contextspecificityof pages 7-8)

Blockquote: A concise verification that C. elegans sek-1 (UniProt G5EDF7) is a dual-specificity MAPKK in the NSY-1→SEK-1→PMK-1/PMK-2 p38 pathway, lists key domains, and warns against cross-species symbol confusion.

Comprehensive research report: sek-1 (UniProt: G5EDF7) in Caenorhabditis elegans

1) Key concepts and definitions (current understanding)
• Molecular identity and domain architecture: sek-1 encodes the C. elegans MAP kinase kinase (MAPKK; MKK3/6 ortholog) in the canonical p38 MAPK module. Genetic and biochemical evidence places SEK-1 downstream of the MAPKKK NSY-1 and upstream of the p38 MAPKs PMK-1 and PMK-2. SEK-1 activity is necessary for PMK-1 activation in vivo; biochemical experiments showed that SEK-1 can phosphorylate and activate p38 when expressed heterologously. These findings are consistent with its classification in the STE Ser/Thr kinase family with a conserved Pkinase catalytic domain and kinase-like fold, supporting dual-specificity MAPKK function (Journal of Biochemistry review, Jul 2004, https://doi.org/10.1093/jb/mvh097; G3, Sep 2017, https://doi.org/10.1534/g3.117.043273) (sakaguchi2004rolesofmap pages 3-4, hoyt2017thesek1p38 pages 1-2).
• Canonical pathway: NSY-1 (MAPKKK) → SEK-1 (MAPKK) → PMK-1/PMK-2 (p38 MAPKs). This module is a central conduit for stress and innate immune signaling, and it is redeployed in neurons for development and behavior. Reviews and genetics place sek-1 as the MKK3/6-like node in this conserved cascade (JBC review, Apr 2016, https://doi.org/10.1074/jbc.r115.711101) (andrusiak2016contextspecificityof pages 7-8, andrusiak2016contextspecificityof pages 3-4, andrusiak2016contextspecificityof pages 4-5).
• Enzymatic role/substrate specificity: As a dual-specificity MAPKK, SEK-1 phosphorylates conserved threonine and tyrosine residues in the activation loop of p38 MAPKs (here PMK-1/PMK-2). In vivo, depletion of sek-1 diminishes PMK-1 phosphorylation during infection, consistent with direct MAPKK function upstream of PMK-1 (Protein & Cell, Dec 2013, https://doi.org/10.1007/s13238-012-2080-z) (xu2013caenorhabditiselegansmom4 pages 2-4).

2) Recent developments and latest research (priority 2023–2024)
• Behavioral plasticity and learning (salt chemotaxis): 2023 genetic dissection shows that NSY-1/SEK-1 signaling in sensory neurons (ASER, ASH, ADF) is required for high-salt attractive learning. Neuronal expression of sek-1 rescued learning defects, whereas immobility was not fully rescued, revealing separable neuronal versus non-neuronal functions. PMK-2 acts partly redundantly with PMK-1 downstream of SEK-1. Reported statistics include ANOVA with ***P < 0.001 and sample sizes of N ≈ 9–15 assays (G3, Jun 2023, https://doi.org/10.1093/g3journal/jkad129) (huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12).
• Chemotherapy/toxin stress (cisplatin): In adult, post-mitotic tissues, cisplatin triggers activation of the p38 MAPK cascade, leading to PMK-1 and ATF-7 phosphorylation and a broad proteomic immune signature. The TIR-1 → NSY-1 → SEK-1 → PMK-1 axis is necessary for resilience to cisplatin; proteomics identified 3,586 proteins with altered abundance (FDR < 0.05), with 121 upregulated >2-fold and 158 downregulated <−2-fold, enriched for innate immune proteins. The authors show SEK-1 is specifically required in adult somatic cells for protection (Nature Communications, May 2023, https://doi.org/10.1038/s41467-023-38568-5) (raj2023cisplatintoxicityis pages 4-7).
• Antimicrobial peptide modulation of p38 signaling: A designed antimicrobial peptide (2K4L) protected C. elegans from Acinetobacter baumannii, dampening infection-induced activation of the p38/PMK-1 pathway. Quantitatively, infection upregulated pathway transcripts (e.g., atf-7 ≈126-fold; pmk-1/skn-1/abf-2 ≈60-fold; tir-1/sek-1/abf-2 ≈4–17-fold), while 2K4L treatment reduced phosphorylated p38 by 40–47% and lowered ROS by ~27–45%, restoring SOD from ~10 to 18–40 U/mg (Scientific Reports, Jul 2024, https://doi.org/10.1038/s41598-024-64511-9) (ji2024antimicrobialpeptide2k4l pages 6-8).
• Contemporary overview in infection biology: A 2024 review synthesizes how the PMK-1/p38 pathway orchestrates responses to Pseudomonas aeruginosa virulence factors and is integrated with redox signaling and metabolic surveillance; although sek-1 is not singled out in the excerpt, it functions as the pathway’s MAPKK (IJMS, Jun 2024, https://doi.org/10.3390/ijms25137034) (hajdu2024modelinghost–pathogeninteractions pages 10-12).

3) Current applications and real-world implementations
• Innate immunity model in vivo: The NSY-1/SEK-1/PMK-1 module is a cornerstone for modeling innate immune defenses against Gram-negative bacteria (e.g., Pseudomonas, Acinetobacter) and for quantifying host resilience to xenobiotics such as cisplatin. Its genetic tractability and phospho-readouts (p-PMK-1) enable mechanism-based evaluation of anti-infective peptides and probiotic/postbiotic interventions (Protein & Cell 2013, https://doi.org/10.1007/s13238-012-2080-z; Sci Rep 2024, https://doi.org/10.1038/s41598-024-64511-9; Nat Commun 2023, https://doi.org/10.1038/s41467-023-38568-5) (xu2013caenorhabditiselegansmom4 pages 2-4, ji2024antimicrobialpeptide2k4l pages 6-8, raj2023cisplatintoxicityis pages 4-7).
• Neuroscience of learning and behavioral modulation: Neuron-specific sek-1 manipulations in defined sensory neurons provide a platform for dissecting learning rules (e.g., salt chemotaxis), circuit-level neuromodulation, and cross-talk with other MAPK branches (G3 2023, https://doi.org/10.1093/g3journal/jkad129) (huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12).

4) Expert opinions and analyses from authoritative sources
• Context-specific deployment: A JBC expert review emphasizes that stress-activated MAPK components are reused in distinct cellular contexts, with SEK-1 operating in the intestine for innate immunity, the epidermis for antifungal defense, and neurons for development and behavior, underscoring modular reuse and cross-talk with JNK modules (JBC, Apr 2016, https://doi.org/10.1074/jbc.r115.711101) (andrusiak2016contextspecificityof pages 7-8, andrusiak2016contextspecificityof pages 3-4, andrusiak2016contextspecificityof pages 4-5).
• Foundational mechanistic placement and biochemical readouts: A Journal of Biochemistry review summarizes genetics and biochemical assays demonstrating that NSY-1, SEK-1, and PMK-1 form a kinase cascade; endogenous PMK-1 activity is reduced in nsy-1 and sek-1 mutants, and SEK-1 can activate p38 in heterologous systems (J Biochem, Jul 2004, https://doi.org/10.1093/jb/mvh097) (sakaguchi2004rolesofmap pages 3-4).

5) Relevant statistics and data from recent studies
• Pathogen survival kinetics: In Pseudomonas aeruginosa PA14 infections, wild-type worms begin to succumb at ≈34 h, whereas hypersusceptible mutants in the p38 module (nsy-1, sek-1, pmk-1) die earlier, ≈16–30 h, demonstrating functional necessity for host defense (JBC, Apr 2016, https://doi.org/10.1074/jbc.r115.711101) (andrusiak2016contextspecificityof pages 3-4, andrusiak2016contextspecificityof pages 4-5).
• PMK-1 phosphorylation assays (in vivo readout of SEK-1 function): RNAi or mutation of sek-1 reduces PMK-1 phosphorylation in response to acute PA14 exposure; experimental conditions include synchronized young adults transferred to PA14 lawns with 3-h exposures before anti-phospho-p38 western blotting (Protein & Cell, Dec 2013, https://doi.org/10.1007/s13238-012-2080-z) (xu2013caenorhabditiselegansmom4 pages 2-4).
• Learning behavior metrics: Salt chemotaxis learning deficits in sek-1 mutants are rescued by neuron-specific sek-1 expression (ASER, ASH, ADF); learning indices exhibit significant restoration with ANOVA ***P < 0.001; typical replicate counts N ≈ 9–15 assays (G3, Jun 2023, https://doi.org/10.1093/g3journal/jkad129) (huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12).
• Cisplatin-evoked proteome remodeling via p38: In adults exposed to cisplatin, 3,586 proteins changed (FDR < 0.05), with 121 >2-fold up and 158 <−2-fold, enriching innate immune categories; PMK-1 and ATF-7 phosphorylation increased, and pathway genetics (tir-1, nsy-1, sek-1, pmk-1) determine resilience (Nat Commun, May 2023, https://doi.org/10.1038/s41467-023-38568-5) (raj2023cisplatintoxicityis pages 4-7).
• Pharmacologic modulation during infection: With Acinetobacter infection, atf-7 shows ≈126-fold induction; pmk-1/skn-1/abf-2 ≈60-fold; tir-1/sek-1/abf-2 ≈4–17-fold. 2K4L reduces p-p38 by 40–47% and lowers ROS by ~27–45%, restoring SOD from ~10 U/mg to 18–40 U/mg (Sci Rep, Jul 2024, https://doi.org/10.1038/s41598-024-64511-9) (ji2024antimicrobialpeptide2k4l pages 6-8).

Functional roles, processes, and localization
• Innate immunity: The NSY-1/SEK-1/PMK-1 module is essential for resistance to bacterial pathogens. sek-1 is required for PMK-1 phosphorylation during infection and for normal survival kinetics on pathogenic lawns, acting predominantly in the intestine for defense gene activation (Protein & Cell 2013, https://doi.org/10.1007/s13238-012-2080-z; JBC 2016, https://doi.org/10.1074/jbc.r115.711101) (xu2013caenorhabditiselegansmom4 pages 2-4, andrusiak2016contextspecificityof pages 4-5, andrusiak2016contextspecificityof pages 3-4).
• Neuronal development and behavior: SEK-1 functions in acetylcholine neurons to modulate locomotion and Gq (EGL-30) signaling; the pathway can suppress hyperactive NCA-1/NALCN, positioning SEK-1 as a modulatory node of neuronal excitability. In learning, SEK-1 acts in ASER/ASH/ADF to promote high-salt attraction after conditioning, with PMK-1/PMK-2 acting redundantly downstream (G3 2017, https://doi.org/10.1534/g3.117.043273; G3 2023, https://doi.org/10.1093/g3journal/jkad129) (hoyt2017thesek1p38 pages 1-2, huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12).
• Epidermal antifungal responses: Reviews synthesize evidence that the same module contributes to epidermal defense during fungal infection (JBC 2016, https://doi.org/10.1074/jbc.r115.711101) (andrusiak2016contextspecificityof pages 4-5).

Evidence summary table
| Claim/Topic | Evidence summary | Pathway position / partners | Tissue / Cell context | Quant / Stats | Year | Source (journal) | DOI / URL | Citation ID |
|---|---|---|---|---|---|---|---|---|
| MAPKK identity & enzymatic role | Genetic/biochemical data identify SEK-1 as an MKK3/6-like MAPKK that activates p38 (PMK) family; SEK-1 expression in mammalian cells phosphorylates/activates p38. | NSY-1 → SEK-1 (MAPKK) → PMK-1 / PMK-2 | Neurons; intestine; epidermis | Endogenous PMK-1 activity reduced in nsy-1 or sek-1 loss-of-function mutants (WB assays) | 2004, 2017 | J Biochem (review); G3 | https://doi.org/10.1093/jb/mvh097, https://doi.org/10.1534/g3.117.043273 | (sakaguchi2004rolesofmap pages 3-4, hoyt2017thesek1p38 pages 1-2) |
| Innate immunity / pathogen resistance | sek-1 required for PMK-1 activation during Pseudomonas aeruginosa infection; sek-1 mutants show enhanced susceptibility (Esp); sek-1 RNAi inhibits p38 activation (anti-phospho-p38 WB). | NSY-1 → SEK-1 → PMK-1 | Intestinal innate immune response | Wild-type begin to succumb ~34 hr on PA14; Esp mutants (nsy-1/sek-1/pmk-1) die ≈16–30 hr | 2013, 2016 | Protein & Cell; JBC | https://doi.org/10.1007/s13238-012-2080-z, https://doi.org/10.1074/jbc.r115.711101 | (xu2013caenorhabditiselegansmom4 pages 2-4, andrusiak2016contextspecificityof pages 7-8) |
| Neuronal role — locomotion & Gq signaling | sek-1 mutants have slow locomotion; SEK-1 acts in acetylcholine neurons to modulate locomotion and Gq (EGL-30) signaling; pathway partially suppresses activated NCA-1/NALCN phenotypes. | TIR-1 → NSY-1 → SEK-1 → PMK-1/PMK-2 | Acetylcholine neurons; mature neurons | Behavioral assays show slowed locomotion and genetic suppression of activated Gq/NCA-1 mutants (qualitative behavioral metrics) | 2017 | G3 | https://doi.org/10.1534/g3.117.043273 | (hoyt2017thesek1p38 pages 1-2) |
| Salt chemotaxis learning (2023) | SEK-1 signaling in sensory neurons (ASER, ASH, ADF) required for high-salt attractive learning; neuronal sek-1 expression rescues learning defect but not immobility. | NSY-1 → SEK-1 → PMK-1 / PMK-2 (PMK-2 partly redundant) | Sensory neurons ASER, ASH, ADF | Reported significance: P < 0.001; N = 9 assays; other assays N = 12–15 | 2023 | G3 | https://doi.org/10.1093/g3journal/jkad129 | (huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12) |
| Context specificity & pathway cross-talk | p38 (NSY-1/SEK-1/PMK-1) and JNK branches are used context-specifically (neuronal development, stress, immunity); SEK-1 participates in AWC asymmetry and behavior with JNK components (e.g., KGB-1). | p38 and JNK modules intersect (e.g., MLK-1/MEK-1/KGB-1) | Neuronal (AWC), intestine, epidermis | Context-specific genetic interactions reported; no single numeric effect size in excerpts | 2016 | Journal of Biological Chemistry (review) | https://doi.org/10.1074/jbc.r115.711101 | (andrusiak2016contextspecificityof pages 7-8, andrusiak2016contextspecificityof pages 3-4, andrusiak2016contextspecificityof pages 4-5) |
| Biochemical activation evidence | sek-1 RNAi/knockout reduces PMK-1 phosphorylation during PA14 infection; activation assayed by anti-phospho-p38 western blots after defined infection/stress exposures. | NSY-1 (MAP3K) upstream; PMK-1 downstream | Intestine (infection assays) | Assay conditions cited (e.g., 3 h transfer to PA14; stressors referenced such as 35°C heat, 200 mM sorbitol, 1200 J UV) | 2013 | Protein & Cell | https://doi.org/10.1007/s13238-012-2080-z | (xu2013caenorhabditiselegansmom4 pages 2-4) |
| Tissue distribution & multi-tissue roles | SEK-1 functions across tissues: intestine (pathogen defense), epidermis (antifungal responses), neurons (development, behavior), and mediates stress responses. | NSY-1 → SEK-1 → PMK-1 module used in multiple tissues | Intestine; epidermis; neurons (AWC, ASER, ASH, ADF) | Esp survival window ≈16–34 hr on pathogen assays; tissue-specific rescue experiments reported | 2004, 2016 | J Biochem (review); JBC | https://doi.org/10.1093/jb/mvh097, https://doi.org/10.1074/jbc.r115.711101 | (sakaguchi2004rolesofmap pages 3-4, andrusiak2016contextspecificityof pages 4-5) |
| Quantitative assay notes & reporting | Recent behavioral studies (Huang 2023) include explicit sample sizes and ANOVA p-values; infection studies report time-to-death windows; biochemical activation quantified via phospho-specific WB. | n/a (methodological) | Neurons (behavioral assays); Intestine (infection assays) | Examples: P < 0.001 (behavioral, N=9); wild-type succumb ≈34 hr on PA14 vs mutants 16–30 hr; phosphorylation assayed after 3 h PA14 exposure | 2016, 2023 | JBC; G3 | https://doi.org/10.1074/jbc.r115.711101, https://doi.org/10.1093/g3journal/jkad129 | (andrusiak2016contextspecificityof pages 3-4, huang2023multiplep38jnkmitogenactivated pages 7-10) |

Table: A concise, cited table summarizing major findings about C. elegans SEK-1 (UniProt G5EDF7): function, pathway partners, tissues, quantitative notes, and source DOIs with context IDs for traceability.

Expert analysis and perspective
SEK-1 is the central MAPKK integrating upstream danger signals (e.g., TIR-1/SARM1- and calcium/CaMKII/UNC-43-dependent activation of NSY-1) with downstream transcriptional programs via PMK-1/PMK-2 and ATF-7/SKN-1. The latest work extends this paradigm from classical infection biology to post-mitotic resilience to chemotherapeutics (cisplatin) and to defined forms of learning (salt chemotaxis), revealing that SEK-1’s context-specific deployment spans epithelial immunity and neuronal plasticity. Quantitative readouts (p-PMK-1 immunoblots, survival curves, behavioral assay statistics, and proteomics) provide convergent, mechanistic support for SEK-1’s role as the activating MAPKK in this pathway (JBC 2016, G3 2017/2023, Nat Commun 2023, Sci Rep 2024) (andrusiak2016contextspecificityof pages 4-5, hoyt2017thesek1p38 pages 1-2, huang2023multiplep38jnkmitogenactivated pages 7-10, raj2023cisplatintoxicityis pages 4-7, ji2024antimicrobialpeptide2k4l pages 6-8).

URLs and publication dates (selection)
• Sakaguchi et al., Journal of Biochemistry, Jul 2004, https://doi.org/10.1093/jb/mvh097 (sakaguchi2004rolesofmap pages 3-4)
• Andrusiak & Jin, Journal of Biological Chemistry, Apr 2016, https://doi.org/10.1074/jbc.r115.711101 (andrusiak2016contextspecificityof pages 7-8, andrusiak2016contextspecificityof pages 3-4, andrusiak2016contextspecificityof pages 4-5)
• Hoyt et al., G3, Sep 2017, https://doi.org/10.1534/g3.117.043273 (hoyt2017thesek1p38 pages 1-2)
• Xu et al., Protein & Cell, Dec 2013, https://doi.org/10.1007/s13238-012-2080-z (xu2013caenorhabditiselegansmom4 pages 2-4)
• Huang et al., G3, Jun 2023, https://doi.org/10.1093/g3journal/jkad129 (huang2023multiplep38jnkmitogenactivated pages 7-10, huang2023multiplep38jnkmitogenactivated pages 12-12)
• Raj et al., Nature Communications, May 2023, https://doi.org/10.1038/s41467-023-38568-5 (raj2023cisplatintoxicityis pages 4-7)
• Ji et al., Scientific Reports, Jul 2024, https://doi.org/10.1038/s41598-024-64511-9 (ji2024antimicrobialpeptide2k4l pages 6-8)
• Hajdú et al., International Journal of Molecular Sciences, Jun 2024, https://doi.org/10.3390/ijms25137034 (hajdu2024modelinghost–pathogeninteractions pages 10-12)

Notes on ambiguity and organism specificity
The sek-1 symbol is used in C. elegans for the p38 MAPKK; mammalian MKK3/6 are homologs but not the research target here. All evidence cited above pertains to the C. elegans sek-1 gene/protein, consistent with the UniProt entry G5EDF7 and its kinase domain architecture (sakaguchi2004rolesofmap pages 3-4, hoyt2017thesek1p38 pages 1-2, andrusiak2016contextspecificityof pages 7-8).

References

(hoyt2017thesek1p38 pages 1-2): Jill M Hoyt, Samuel K Wilson, Madhuri Kasa, Jeremy S Rise, Irini Topalidou, and Michael Ailion. The sek-1 p38 map kinase pathway modulates gq signaling incaenorhabditis elegans. G3 Genes|Genomes|Genetics, 7:2979-2989, Sep 2017. URL: https://doi.org/10.1534/g3.117.043273, doi:10.1534/g3.117.043273. This article has 22 citations.
(sakaguchi2004rolesofmap pages 3-4): A. Sakaguchi, Kunihiro Matsumoto, and N. Hisamoto. Roles of map kinase cascades in caenorhabditis elegans. Journal of biochemistry, 136 1:7-11, Jul 2004. URL: https://doi.org/10.1093/jb/mvh097, doi:10.1093/jb/mvh097. This article has 84 citations and is from a peer-reviewed journal.
(andrusiak2016contextspecificityof pages 7-8): Matthew G. Andrusiak and Yishi Jin. Context specificity of stress-activated mitogen-activated protein (map) kinase signaling: the story as told by caenorhabditis elegans. Journal of Biological Chemistry, 291:7796-7804, Apr 2016. URL: https://doi.org/10.1074/jbc.r115.711101, doi:10.1074/jbc.r115.711101. This article has 69 citations and is from a domain leading peer-reviewed journal.
(andrusiak2016contextspecificityof pages 3-4): Matthew G. Andrusiak and Yishi Jin. Context specificity of stress-activated mitogen-activated protein (map) kinase signaling: the story as told by caenorhabditis elegans. Journal of Biological Chemistry, 291:7796-7804, Apr 2016. URL: https://doi.org/10.1074/jbc.r115.711101, doi:10.1074/jbc.r115.711101. This article has 69 citations and is from a domain leading peer-reviewed journal.
(andrusiak2016contextspecificityof pages 4-5): Matthew G. Andrusiak and Yishi Jin. Context specificity of stress-activated mitogen-activated protein (map) kinase signaling: the story as told by caenorhabditis elegans. Journal of Biological Chemistry, 291:7796-7804, Apr 2016. URL: https://doi.org/10.1074/jbc.r115.711101, doi:10.1074/jbc.r115.711101. This article has 69 citations and is from a domain leading peer-reviewed journal.
(xu2013caenorhabditiselegansmom4 pages 2-4): Ajing Xu, Guojun Shi, Feng Liu, and Baoxue Ge. Caenorhabditis elegans mom-4 is required for the activation of the p38 mapk signaling pathway in the response to pseudomonas aeruginosa infection. Protein & Cell, 4:53-61, Dec 2013. URL: https://doi.org/10.1007/s13238-012-2080-z, doi:10.1007/s13238-012-2080-z. This article has 16 citations and is from a peer-reviewed journal.
(huang2023multiplep38jnkmitogenactivated pages 7-10): Taoruo Huang, Kota Suzuki, Hirofumi Kunitomo, Masahiro Tomioka, and Yuichi Iino. Multiple p38/jnk mitogen-activated protein kinase (mapk) signaling pathways mediate salt chemotaxis learning in c. elegans. G3: Genes, Genomes, Genetics, Jun 2023. URL: https://doi.org/10.1093/g3journal/jkad129, doi:10.1093/g3journal/jkad129. This article has 5 citations and is from a domain leading peer-reviewed journal.
(huang2023multiplep38jnkmitogenactivated pages 12-12): Taoruo Huang, Kota Suzuki, Hirofumi Kunitomo, Masahiro Tomioka, and Yuichi Iino. Multiple p38/jnk mitogen-activated protein kinase (mapk) signaling pathways mediate salt chemotaxis learning in c. elegans. G3: Genes, Genomes, Genetics, Jun 2023. URL: https://doi.org/10.1093/g3journal/jkad129, doi:10.1093/g3journal/jkad129. This article has 5 citations and is from a domain leading peer-reviewed journal.
(raj2023cisplatintoxicityis pages 4-7): Dorota Raj, Bashar Kraish, Jari Martikainen, Agnieszka Podraza-Farhanieh, Gautam Kao, and Peter Naredi. Cisplatin toxicity is counteracted by the activation of the p38/atf-7 signaling pathway in post-mitotic c. elegans. Nature Communications, May 2023. URL: https://doi.org/10.1038/s41467-023-38568-5, doi:10.1038/s41467-023-38568-5. This article has 12 citations and is from a highest quality peer-reviewed journal.
(ji2024antimicrobialpeptide2k4l pages 6-8): Fangyu Ji, Guoxu Tian, and Dejing Shang. Antimicrobial peptide 2k4l inhibits the inflammatory response in macrophages and caenorhabditis elegans and protects against lps-induced septic shock in mice. Scientific Reports, Jul 2024. URL: https://doi.org/10.1038/s41598-024-64511-9, doi:10.1038/s41598-024-64511-9. This article has 1 citations and is from a peer-reviewed journal.
(hajdu2024modelinghost–pathogeninteractions pages 10-12): Gábor Hajdú, Csenge Szathmári, and Csaba Sőti. Modeling host–pathogen interactions in c. elegans: lessons learned from pseudomonas aeruginosa infection. International Journal of Molecular Sciences, 25:7034, Jun 2024. URL: https://doi.org/10.3390/ijms25137034, doi:10.3390/ijms25137034. This article has 11 citations and is from a poor quality or predatory journal.

Citations

sakaguchi2004rolesofmap pages 3-4
andrusiak2016contextspecificityof pages 7-8
raj2023cisplatintoxicityis pages 4-7
andrusiak2016contextspecificityof pages 4-5
andrusiak2016contextspecificityof pages 3-4
https://doi.org/10.1093/jb/mvh097;
https://doi.org/10.1534/g3.117.043273
https://doi.org/10.1074/jbc.r115.711101
https://doi.org/10.1007/s13238-012-2080-z
https://doi.org/10.1093/g3journal/jkad129
https://doi.org/10.1038/s41467-023-38568-5
https://doi.org/10.1038/s41598-024-64511-9
https://doi.org/10.3390/ijms25137034
https://doi.org/10.1007/s13238-012-2080-z;
https://doi.org/10.1038/s41598-024-64511-9;
https://doi.org/10.1093/jb/mvh097
https://doi.org/10.1534/g3.117.043273;
https://doi.org/10.1093/jb/mvh097,
https://doi.org/10.1007/s13238-012-2080-z,
https://doi.org/10.1074/jbc.r115.711101,
https://doi.org/10.1534/g3.117.043273,
https://doi.org/10.1093/g3journal/jkad129,
https://doi.org/10.1038/s41467-023-38568-5,
https://doi.org/10.1038/s41598-024-64511-9,
https://doi.org/10.3390/ijms25137034,

📄 View Raw YAML

id: G5EDF7
gene_symbol: sek-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: 'SEK-1 is a dual-specificity mitogen-activated protein kinase kinase
  (MAPKK) that functions as a central component of the conserved p38 MAPK signaling
  cascade (nsy-1 -> sek-1 -> pmk-1). This kinase phosphorylates and activates PMK-1
  (the C. elegans p38 MAPK ortholog) on both serine/threonine and tyrosine residues.
  SEK-1 plays essential roles in two major biological processes: (1) innate immune
  responses against bacterial and fungal pathogens, where it activates PMK-1-dependent
  transcription of antimicrobial peptides and stress response genes; and (2) asymmetric
  neuronal cell fate determination in the AWC olfactory neurons, where it acts downstream
  of calcium/CaMKII signaling to repress str-2 expression. SEK-1 is also involved
  in oxidative stress responses via PMK-1-mediated nuclear localization of SKN-1 and
  stabilization of RNT-1. The protein is activated by NSY-1 (MAPKKK)-mediated phosphorylation
  at Ser-204 and Thr-208.'
existing_annotations:
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SEK-1 is definitively part of the p38 MAPK cascade, functioning 
      between NSY-1 (MAPKKK) and PMK-1 (p38 MAPK). This has been demonstrated in
      multiple studies showing the signaling hierarchy (PMID:11751572, 
      PMID:12142542). The phylogenetic inference from PAINT is consistent with 
      experimental data.
    action: ACCEPT
    reason: Core function well-established by multiple experimental studies. 
      SEK-1 is the direct MAPKK in the conserved p38 cascade.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: RNA interference assays and biochemical analysis 
        established that a p38 ortholog, pmk-1, functions as the downstream MAP 
        kinase required for pathogen defense
    - reference_id: PMID:11751572
      supporting_text: the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ 
        signaling through CaMKII
    - reference_id: file:worm/sek-1/sek-1-deep-research-falcon.md
      supporting_text: 'model: Edison Scientific Literature'
- term:
    id: GO:0004708
    label: MAP kinase kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SEK-1 has demonstrated MAP kinase kinase activity, phosphorylating 
      PMK-1/p38 on both serine/threonine and tyrosine residues (PMID:11751572). 
      The IBA annotation accurately reflects this core molecular function.
    action: ACCEPT
    reason: Core molecular function supported by direct biochemical evidence. 
      SEK-1 phosphorylates and activates PMK-1 (p38 MAPK).
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal
        asymmetric development
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: This IEA annotation from ARBA machine learning correctly identifies
      SEK-1's role in the MAPK cascade. It is consistent with the more specific 
      IBA annotation and extensive experimental evidence.
    action: ACCEPT
    reason: Accurate automated annotation consistent with experimental evidence.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: As a kinase, SEK-1 requires nucleotide binding for catalytic 
      activity. However, this is a very general term; ATP binding (GO:0005524) 
      would be more informative.
    action: ACCEPT
    reason: Accurate but very general annotation for a kinase. The more specific
      ATP binding annotation is also present.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: SEK-1 has protein kinase activity as demonstrated by its ability to
      phosphorylate PMK-1. However, this is a broad term; more specific terms 
      like MAP kinase kinase activity are more informative.
    action: ACCEPT
    reason: Accurate parent term for the more specific MAP kinase kinase 
      activity.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: SEK-1 phosphorylates PMK-1 on serine and threonine residues as part
      of its dual-specificity kinase activity. This annotation is accurate.
    action: ACCEPT
    reason: Component of the dual-specificity kinase activity demonstrated for 
      SEK-1.
- term:
    id: GO:0004708
    label: MAP kinase kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: EC-based annotation correctly identifies SEK-1's MAP kinase kinase 
      activity (EC 2.7.12.2). This is consistent with experimental evidence.
    action: ACCEPT
    reason: Accurate annotation based on enzyme classification, supported by 
      experimental data.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: SEK-1 is a dual-specificity kinase that phosphorylates tyrosine in 
      addition to serine/threonine. This annotation is accurate for a MAPKK.
    action: ACCEPT
    reason: Component of dual-specificity kinase activity characteristic of 
      MAPKKs.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Kinases require ATP as a phosphate donor. The UniProt record 
      indicates ATP binding at residues 56-64 and K79.
    action: ACCEPT
    reason: Essential for kinase activity; supported by sequence analysis.
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: SEK-1 is involved in AWC neuronal asymmetric development 
      (PMID:11751572). This general term is accurate but non-specific.
    action: KEEP_AS_NON_CORE
    reason: While accurate, the more specific term 'determination of left/right 
      asymmetry in nervous system' (GO:0035545) better captures SEK-1's role.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Very broad parent term; more specific kinase activity terms are 
      present.
    action: ACCEPT
    reason: Accurate parent term in the kinase hierarchy.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Very broad parent term for kinase activity.
    action: ACCEPT
    reason: Accurate but very general parent term.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Kinases typically require Mg2+ as a cofactor for ATP hydrolysis. 
      This is a standard requirement for protein kinases.
    action: ACCEPT
    reason: Accurate; metal ion binding (Mg2+) is required as cofactor for 
      kinase activity.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: SEK-1 phosphorylates serine residues on its substrates. This is 
      part of its dual-specificity kinase function.
    action: ACCEPT
    reason: Component of dual-specificity kinase activity.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IGI
  original_reference_id: PMID:22308034
  review:
    summary: This study demonstrates SEK-1's role in the MAPK cascade in the 
      context of oxidative stress response and RNT-1 stabilization. The IGI 
      evidence with PMK-1 (Q17446) is appropriate.
    action: ACCEPT
    reason: Well-supported by genetic interaction data in oxidative stress 
      context.
    supported_by:
    - reference_id: PMID:22308034
      supporting_text: The MAP kinase pathway is required for RNT-1 
        stabilization, and RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:20008556
  review:
    summary: This study examined MAPK pathways in stress response. While the 
      paper primarily focuses on the JNK pathway (MLK-1-MEK-1-KGB-1), it 
      provides context for MAPK signaling that includes the p38 pathway.
    action: ACCEPT
    reason: IMP evidence for MAPK cascade involvement, though the paper 
      emphasizes JNK pathway.
    supported_by:
    - reference_id: PMID:20008556
      supporting_text: Dec 14. The Caenorhabditis elegans Ste20-related kinase 
        and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling
        pathway mediating the stress response.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17888400
  review:
    summary: This study shows that SEK-1 is required for pgp-5 transcriptional 
      induction in response to bacterial infection, which requires TIR-1 and the
      p38 MAPK cascade.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream consequence of SEK-1's role in the p38 cascade 
      rather than a core function. The transcriptional activation is mediated by
      downstream transcription factors like SKN-1.
    supported_by:
    - reference_id: PMID:17888400
      supporting_text: pgp-5 is induced by both bacterial infection and heavy 
        metal stress
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:17888400
  review:
    summary: SEK-1 is required for resistance to Pseudomonas aeruginosa 
      infection. The p38 MAPK pathway (including SEK-1) mediates innate immune 
      responses against Gram-negative bacteria.
    action: ACCEPT
    reason: Core function of SEK-1 in innate immunity is well-established. 
      Multiple studies confirm this role (PMID:12142542, PMID:17888400, 
      PMID:19454349).
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: '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'
    - reference_id: PMID:17888400
      supporting_text: signals from both biotic and abiotic stresses are 
        integrated by TIR-1... and a p38 MAP kinase signaling cassette
- term:
    id: GO:1902236
    label: negative regulation of endoplasmic reticulum stress-induced intrinsic
      apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:21857923
  review:
    summary: This study demonstrates that SEK-1/PMK-1 signaling protects against
      ER stress and dopaminergic neuron degeneration in the context of LRRK2 
      signaling. The sek-1 mutant shows enhanced sensitivity to 6-OHDA-induced 
      neurotoxicity.
    action: KEEP_AS_NON_CORE
    reason: This represents a specific context (dopaminergic neuron protection, 
      LRRK2 pathway) rather than a core function of SEK-1. The term is quite 
      specific to this study.
    supported_by:
    - reference_id: PMID:21857923
      supporting_text: nematodes with a loss-of-function mutation in sek-1 
        consistently displayed enhanced susceptibility to 6-OHDA-induced 
        neurotoxicity
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11751572
  review:
    summary: This is direct biochemical evidence for SEK-1's dual-specificity 
      kinase activity. The paper demonstrates that SEK-1 phosphorylates PMK-1 on
      both Ser/Thr and Tyr residues.
    action: ACCEPT
    reason: Core molecular function with direct experimental evidence. This 
      accurately describes SEK-1 as a dual-specificity MAPKK.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal
        asymmetric development
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:22308034
  review:
    summary: SEK-1 is required for stabilization of RNT-1 during oxidative 
      stress and for the oxidative stress response mediated through PMK-1 and 
      SKN-1.
    action: ACCEPT
    reason: Important function of the p38 cascade in C. elegans oxidative stress
      response.
    supported_by:
    - reference_id: PMID:22308034
      supporting_text: RNT-1 was rapidly stabilized by oxidative stress... The 
        MAP kinase pathway is required for RNT-1 stabilization
    - reference_id: PMID:16166371
      supporting_text: The C. elegans p38 MAPK pathway regulates nuclear 
        localization of the transcription factor SKN-1 in oxidative stress 
        response
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IGI
  original_reference_id: PMID:22308034
  review:
    summary: Genetic interaction with PMK-1 supports SEK-1's serine kinase 
      activity in the context of RNT-1 phosphorylation during oxidative stress.
    action: ACCEPT
    reason: Supports the biochemical evidence for SEK-1 kinase activity.
    supported_by:
    - reference_id: PMID:22308034
      supporting_text: RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro
- term:
    id: GO:0140367
    label: antibacterial innate immune response
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: This seminal paper established SEK-1's role in innate immunity 
      against bacterial pathogens. sek-1 mutants show enhanced susceptibility to
      killing by P. aeruginosa and other pathogens.
    action: ACCEPT
    reason: Core function of SEK-1 in innate immunity, established in the 
      foundational paper for this pathway.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: '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'
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:22470487
  review:
    summary: SEK-1 is required for induction of antimicrobial peptide gene 
      expression (nlp-29 cluster) following fungal infection. This is a 
      downstream effect of the p38 cascade.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream consequence of SEK-1's signaling role rather 
      than a core function. The annotation to immune response is more 
      informative.
    supported_by:
    - reference_id: PMID:22470487
      supporting_text: inductive signaling passes via TPA-1... and a MAPK 
        cassette comprising the MAP3K NSY-1, the MAP2K SEK-1, and PMK-1
- term:
    id: GO:0050832
    label: defense response to fungus
  evidence_type: IMP
  original_reference_id: PMID:22470487
  review:
    summary: SEK-1 is required for antimicrobial peptide gene induction 
      following infection with the fungus Drechmeria coniospora. This expands 
      the innate immune function beyond bacteria.
    action: ACCEPT
    reason: Important extension of SEK-1's innate immune function to fungal 
      pathogens.
    supported_by:
    - reference_id: PMID:22470487
      supporting_text: inductive signaling passes via TPA-1... and a MAPK 
        cassette comprising the MAP3K NSY-1, the MAP2K SEK-1, and PMK-1... We 
        have shown that for nlp-29 cluster genes, following both infection and 
        injury
- term:
    id: GO:0004708
    label: MAP kinase kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11751572
  review:
    summary: Direct biochemical demonstration of SEK-1's MAPKK activity, showing
      it phosphorylates and activates PMK-1.
    action: ACCEPT
    reason: Core molecular function with direct experimental evidence.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal
        asymmetric development
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:25274306
  review:
    summary: This study on mitochondrial UPR shows that pre-activation of UPR 
      enhances survival of sek-1 mutants exposed to P. aeruginosa, confirming 
      SEK-1's role in defense against Gram-negative bacteria.
    action: ACCEPT
    reason: Additional evidence supporting SEK-1's role in defense against 
      Gram-negative pathogens.
    supported_by:
    - reference_id: PMID:25274306
      supporting_text: pre-activation of the UPRmt enhanced the survival of the 
        pmk-1 and sek-1 mutants
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IGI
  original_reference_id: PMID:25274306
  review:
    summary: Genetic interaction with ATFS-1 in the context of P. aeruginosa 
      defense supports SEK-1's role in innate immunity.
    action: ACCEPT
    reason: Genetic interaction data supporting SEK-1's immune function.
    supported_by:
    - reference_id: PMID:25274306
      supporting_text: pre-activation of the UPRmt enhanced the survival of the 
        pmk-1 and sek-1 mutants
- term:
    id: GO:0050830
    label: defense response to Gram-positive bacterium
  evidence_type: IMP
  original_reference_id: PMID:24972867
  review:
    summary: This study shows SEK-1 is required for protection against 
      Staphylococcus aureus infection. The p38 MAP kinase pathway mediates the 
      protective effect.
    action: ACCEPT
    reason: Extends SEK-1's innate immune function to Gram-positive pathogens.
    supported_by:
    - reference_id: PMID:24972867
      supporting_text: The effect of UE-12 is diminished in sek-1 (km4) and 
        pmk-1 (km25) mutants... the p38 MAP kinase and insulin-like signaling 
        pathways
- term:
    id: GO:0009636
    label: response to toxic substance
  evidence_type: IMP
  original_reference_id: PMID:21408619
  review:
    summary: This study on cellular responses to pore-forming toxins shows that 
      the p38 MAPK pathway (including SEK-1) is important for defense against 
      bacterial toxins.
    action: KEEP_AS_NON_CORE
    reason: Related to innate immunity function but very general. More specific 
      defense response annotations are present.
    supported_by:
    - reference_id: PMID:21408619
      supporting_text: the p38 mitogen-activated protein kinase (MAPK) pathway 
        was the first intracellular pathway demonstrated to protect cells 
        against PFTs
- term:
    id: GO:0093002
    label: response to nematicide
  evidence_type: IMP
  original_reference_id: PMID:15256590
  review:
    summary: SEK-1 is required for defense against bacterial pore-forming toxins
      like Cry5B from Bacillus thuringiensis. sek-1 is transcriptionally 
      upregulated by Cry5B and mutants are hypersensitive to the toxin.
    action: ACCEPT
    reason: Important function in response to natural nematode pathogens/toxins.
    supported_by:
    - reference_id: PMID:15256590
      supporting_text: A p38 mitogen-activated protein kinase (MAPK) kinase and 
        a c-Jun N-terminal-like MAPK are both transcriptionally up-regulated by 
        Cry5B
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IGI
  original_reference_id: PMID:11751572
  review:
    summary: Genetic interactions with nsy-1 (MAPKKK) and pmk-1 (MAPK) establish
      SEK-1's position in the MAPK cascade.
    action: ACCEPT
    reason: Foundational genetic evidence for SEK-1's role in the p38 cascade.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ 
        signaling through CaMKII
- term:
    id: GO:0031435
    label: mitogen-activated protein kinase kinase kinase binding
  evidence_type: IPI
  original_reference_id: PMID:11751572
  review:
    summary: SEK-1 physically interacts with NSY-1 (MAPKKK). This interaction is
      essential for pathway function.
    action: ACCEPT
    reason: Direct protein interaction evidence for SEK-1-NSY-1 binding.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 functions in a pathway downstream of UNC-43 and 
        NSY-1
- term:
    id: GO:0034607
    label: turning behavior involved in mating
  evidence_type: IMP
  original_reference_id: PMID:11751572
  review:
    summary: sek-1 mutants show defects in male mating behavior, likely related 
      to neuronal signaling functions.
    action: KEEP_AS_NON_CORE
    reason: This is likely a pleiotropic effect of the neuronal asymmetry 
      function rather than a core function.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal
        asymmetric development in Caenorhabditis elegans.
- term:
    id: GO:0035545
    label: determination of left/right asymmetry in nervous system
  evidence_type: IMP
  original_reference_id: PMID:11751572
  review:
    summary: SEK-1 is essential for establishing asymmetric cell fates in the 
      AWC olfactory neurons. This is one of the two major biological roles of 
      SEK-1.
    action: ACCEPT
    reason: Core function of SEK-1 in neuronal development, established in the 
      foundational paper.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 is required for asymmetric expression in AWC 
        neurons... the NSY-1-SEK-1-MAPK cascade is activated by Ca2+ signaling 
        through CaMKII and establishes asymmetric cell fate decision during 
        neuronal development
- term:
    id: GO:0035545
    label: determination of left/right asymmetry in nervous system
  evidence_type: IGI
  original_reference_id: PMID:11751572
  review:
    summary: Genetic interaction with nsy-1 in the context of AWC asymmetry 
      supports this annotation.
    action: ACCEPT
    reason: Genetic evidence supporting the neuronal asymmetry function.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: Genetic and biochemical analyses reveal that SEK-1 
        functions in a pathway downstream of UNC-43 and NSY-1
- term:
    id: GO:0046662
    label: regulation of egg-laying behavior
  evidence_type: IMP
  original_reference_id: PMID:11751572
  review:
    summary: sek-1 mutants show egg-laying defects. The UniProt record notes 
      "Egg-laying defect" for the G212R mutant.
    action: KEEP_AS_NON_CORE
    reason: This is likely a pleiotropic effect rather than a core function.
    supported_by:
    - reference_id: PMID:11751572
      supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal
        asymmetric development in Caenorhabditis elegans.
- term:
    id: GO:0050830
    label: defense response to Gram-positive bacterium
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: The foundational paper showed sek-1 mutants have enhanced 
      susceptibility to Enterococcus faecalis (Gram-positive).
    action: ACCEPT
    reason: Core innate immunity function established in the foundational paper.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: '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'
- term:
    id: GO:0038066
    label: p38MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: This is the most specific term for SEK-1's role in the MAPK 
      cascade. The paper establishes SEK-1 as a component of the conserved p38 
      MAPK pathway.
    action: ACCEPT
    reason: Most appropriate specific term for SEK-1's signaling function.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: RNA interference assays and biochemical analysis 
        established that a p38 ortholog, pmk-1, functions as the downstream MAP 
        kinase
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: sek-1 was identified in a screen for mutants with enhanced 
      susceptibility to P. aeruginosa (Gram-negative).
    action: ACCEPT
    reason: Core innate immunity function from the foundational study.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: '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'
- term:
    id: GO:1901046
    label: positive regulation of egg-laying behavior
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: sek-1 mutants show reduced egg-laying. This annotation is more 
      specific than 'regulation of egg-laying behavior'.
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic effect; not a core function of SEK-1.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: A conserved p38 MAP kinase pathway in Caenorhabditis 
        elegans innate immunity.
- term:
    id: GO:0000302
    label: response to reactive oxygen species
  evidence_type: IMP
  original_reference_id: PMID:16166371
  review:
    summary: SEK-1/PMK-1 pathway regulates SKN-1 nuclear localization during 
      oxidative stress. gcs-1 expression in response to arsenite requires this 
      pathway.
    action: ACCEPT
    reason: Important stress response function linked to core p38 signaling.
    supported_by:
    - reference_id: PMID:16166371
      supporting_text: The C. elegans p38 MAPK pathway regulates nuclear 
        localization of the transcription factor SKN-1 in oxidative stress 
        response
- term:
    id: GO:0000303
    label: response to superoxide
  evidence_type: IMP
  original_reference_id: PMID:16166371
  review:
    summary: More specific child term of response to ROS. The p38 pathway 
      responds to oxidative stress including superoxide.
    action: ACCEPT
    reason: Specific oxidative stress response function.
    supported_by:
    - reference_id: PMID:16166371
      supporting_text: In response to oxidative stress, PMK-1 phosphorylates 
        SKN-1
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IMP
  original_reference_id: PMID:19454349
  review:
    summary: SEK-1 is required for conditioning-mediated protection against 
      enteropathogenic E. coli. The p38 MAPK pathway mediates this innate immune
      response.
    action: ACCEPT
    reason: Core innate immunity function.
    supported_by:
    - reference_id: PMID:19454349
      supporting_text: Conditioning requires dopaminergic neurons; the p38 MAP 
        kinase pathway, which regulates innate immunity
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:19454349
  review:
    summary: Protection against enteropathogenic E. coli requires SEK-1/PMK-1 
      signaling.
    action: ACCEPT
    reason: Additional evidence for innate immune function against Gram-negative
      bacteria.
    supported_by:
    - reference_id: PMID:19454349
      supporting_text: Conditioning requires... the p38 MAP kinase pathway, 
        which regulates innate immunity
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IMP
  original_reference_id: PMID:12142542
  review:
    summary: Foundational evidence for SEK-1's role in innate immunity. sek-1 
      mutants show enhanced susceptibility to multiple pathogens.
    action: ACCEPT
    reason: Core function established in the seminal paper.
    supported_by:
    - reference_id: PMID:12142542
      supporting_text: A conserved p38 MAP kinase pathway in Caenorhabditis 
        elegans innate immunity
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11751572
  title: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric 
    development in Caenorhabditis elegans.
  findings:
  - statement: SEK-1 is required for asymmetric expression of str-2 in AWC 
      neurons
    supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal 
      asymmetric development in Caenorhabditis elegans.
  - statement: SEK-1 functions downstream of UNC-43 (CaMKII) and NSY-1 (MAPKKK)
    supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal 
      asymmetric development in Caenorhabditis elegans.
  - statement: SEK-1 interacts with NSY-1
    supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal 
      asymmetric development in Caenorhabditis elegans.
  - statement: Demonstrates dual-specificity kinase activity
    supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal 
      asymmetric development in Caenorhabditis elegans.
  - statement: Activated by phosphorylation at Ser-204 and Thr-208
    supporting_text: SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal 
      asymmetric development in Caenorhabditis elegans.
- id: PMID:12142542
  title: A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate 
    immunity.
  findings:
  - statement: sek-1 identified in screen for enhanced susceptibility to P. 
      aeruginosa
    supporting_text: A conserved p38 MAP kinase pathway in Caenorhabditis 
      elegans innate immunity.
  - statement: nsy-1/sek-1/pmk-1 form conserved p38 MAPK pathway for pathogen 
      defense
    supporting_text: A conserved p38 MAP kinase pathway in Caenorhabditis 
      elegans innate immunity.
  - statement: sek-1 mutants hypersensitive to bacterial pathogens
    supporting_text: A conserved p38 MAP kinase pathway in Caenorhabditis 
      elegans innate immunity.
- id: PMID:15256590
  title: Mitogen-activated protein kinase pathways defend against bacterial 
    pore-forming toxins.
  findings:
  - statement: p38 MAPK pathway required for defense against Cry5B toxin
    supporting_text: Mitogen-activated protein kinase pathways defend against 
      bacterial pore-forming toxins.
  - statement: sek-1 transcriptionally upregulated by Cry5B
    supporting_text: Mitogen-activated protein kinase pathways defend against 
      bacterial pore-forming toxins.
- id: PMID:16166371
  title: The C. elegans p38 MAPK pathway regulates nuclear localization of the 
    transcription factor SKN-1 in oxidative stress response.
  findings:
  - statement: p38 pathway regulates SKN-1 nuclear localization during oxidative
      stress
    supporting_text: The C. elegans p38 MAPK pathway regulates nuclear 
      localization of the transcription factor SKN-1 in oxidative stress 
      response.
  - statement: gcs-1 expression requires p38 pathway
    supporting_text: The C. elegans p38 MAPK pathway regulates nuclear 
      localization of the transcription factor SKN-1 in oxidative stress 
      response.
- id: PMID:17888400
  title: 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.
  findings:
  - statement: pgp-5 induction requires TIR-1 and p38 cascade including SEK-1
    supporting_text: 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.
- id: PMID:19454349
  title: Conditioning protects C. elegans from lethal effects of 
    enteropathogenic E. coli by activating genes that regulate lifespan and 
    innate immunity.
  findings:
  - statement: Conditioning protection requires p38 MAP kinase pathway
    supporting_text: Conditioning protects C. elegans from lethal effects of 
      enteropathogenic E. coli by activating genes that regulate lifespan and 
      innate immunity.
- id: PMID:20008556
  title: The Caenorhabditis elegans Ste20-related kinase and Rac-type small 
    GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the 
    stress response.
  findings:
  - statement: Context for MAPK signaling in stress response
    supporting_text: The Caenorhabditis elegans Ste20-related kinase and 
      Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling 
      pathway mediating the stress response.
- id: PMID:21408619
  title: Global functional analyses of cellular responses to pore-forming 
    toxins.
  findings:
  - statement: p38 MAPK pathway important for defense against pore-forming 
      toxins
    supporting_text: Global functional analyses of cellular responses to 
      pore-forming toxins.
- id: PMID:21857923
  title: Dysregulated LRRK2 signaling in response to endoplasmic reticulum 
    stress leads to dopaminergic neuron degeneration in C. elegans.
  findings:
  - statement: sek-1 mutants show enhanced sensitivity to 6-OHDA neurotoxicity
    supporting_text: Dysregulated LRRK2 signaling in response to endoplasmic 
      reticulum stress leads to dopaminergic neuron degeneration in C. elegans.
  - statement: sek-1 functions in same pathway as lrk-1 and pmk-1
    supporting_text: Dysregulated LRRK2 signaling in response to endoplasmic 
      reticulum stress leads to dopaminergic neuron degeneration in C. elegans.
- id: PMID:22308034
  title: Stabilization of RNT-1 protein, runt-related transcription factor 
    (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress 
    through mitogen-activated protein kinase pathway.
  findings:
  - statement: RNT-1 phosphorylated by SEK-1/PMK-1 in vitro
    supporting_text: Stabilization of RNT-1 protein, runt-related transcription 
      factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative 
      stress through mitogen-activated protein kinase pathway.
  - statement: MAP kinase pathway required for RNT-1 stabilization during 
      oxidative stress
    supporting_text: Stabilization of RNT-1 protein, runt-related transcription 
      factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative 
      stress through mitogen-activated protein kinase pathway.
- id: PMID:22470487
  title: The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide 
    gene expression.
  findings:
  - statement: SEK-1 part of MAPK cassette for nlp-29 induction
    supporting_text: The pseudokinase NIPI-4 is a novel regulator of 
      antimicrobial peptide gene expression.
  - statement: Required for antimicrobial peptide expression after fungal 
      infection
    supporting_text: The pseudokinase NIPI-4 is a novel regulator of 
      antimicrobial peptide gene expression.
- id: PMID:24972867
  title: Orthosiphon stamineus protects Caenorhabditis elegans against 
    Staphylococcus aureus infection through immunomodulation.
  findings:
  - statement: SEK-1 required for p38 MAPK-mediated protection against S. aureus
    supporting_text: Orthosiphon stamineus protects Caenorhabditis elegans 
      against Staphylococcus aureus infection through immunomodulation.
- id: PMID:25274306
  title: Mitochondrial UPR-regulated innate immunity provides resistance to 
    pathogen infection.
  findings:
  - statement: UPRmt pre-activation enhances survival of sek-1 mutants during P.
      aeruginosa infection
    supporting_text: Mitochondrial UPR-regulated innate immunity provides 
      resistance to pathogen infection.
  - statement: UPRmt can function independently of NSY-1/SEK-1/PMK-1 pathway
    supporting_text: Mitochondrial UPR-regulated innate immunity provides 
      resistance to pathogen infection.
- id: file:worm/sek-1/sek-1-deep-research-falcon.md
  title: Deep research report on sek-1
  findings: []
core_functions:
- description: Direct biochemical evidence (IDA, PMID:11751572) demonstrates 
    SEK-1 phosphorylates and activates PMK-1 (p38 MAPK). SEK-1 is a 
    dual-specificity kinase phosphorylating both serine/threonine and tyrosine 
    residues.
  molecular_function:
    id: GO:0004708
    label: MAP kinase kinase activity
  directly_involved_in:
  - id: GO:0038066
    label: p38MAPK cascade
- description: sek-1 mutants show enhanced susceptibility to multiple bacterial 
    pathogens including P. aeruginosa, E. faecalis, and S. aureus 
    (PMID:12142542, PMID:24972867).
  molecular_function:
    id: GO:0004708
    label: MAP kinase kinase activity
  directly_involved_in:
  - id: GO:0140367
    label: antibacterial innate immune response
- description: SEK-1 is required for asymmetric cell fate determination in AWC 
    olfactory neurons, acting downstream of calcium/CaMKII signaling 
    (PMID:11751572).
  molecular_function:
    id: GO:0004708
    label: MAP kinase kinase activity
  directly_involved_in:
  - id: GO:0035545
    label: determination of left/right asymmetry in nervous system
- description: SEK-1/PMK-1 pathway regulates SKN-1 nuclear localization and 
    RNT-1 stabilization during oxidative stress (PMID:16166371, PMID:22308034).
  molecular_function:
    id: GO:0004708
    label: MAP kinase kinase activity
  directly_involved_in:
  - id: GO:0006979
    label: response to oxidative stress
tags:
- caeel-surveillance-immunity

sek-1

Gene Description

Existing Annotations Review

Core Functions

Direct biochemical evidence (IDA, PMID:11751572) demonstrates SEK-1 phosphorylates and activates PMK-1 (p38 MAPK). SEK-1 is a dual-specificity kinase phosphorylating both serine/threonine and tyrosine residues.

sek-1 mutants show enhanced susceptibility to multiple bacterial pathogens including P. aeruginosa, E. faecalis, and S. aureus (PMID:12142542, PMID:24972867).

SEK-1 is required for asymmetric cell fate determination in AWC olfactory neurons, acting downstream of calcium/CaMKII signaling (PMID:11751572).

SEK-1/PMK-1 pathway regulates SKN-1 nuclear localization and RNT-1 stabilization during oxidative stress (PMID:16166371, PMID:22308034).

References

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Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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MANDATORY VERIFICATION STEPS:

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