mpk-1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000165 MAPK cascade	IMP PMID:15268855 The ERK MAP kinase cascade mediates tail swelling and a prot...	ACCEPT	Summary: MPK-1 is the terminal ERK kinase in a conserved C. elegans MAPK cascade. Reason: MPK-1 is the C. elegans ERK/MAP kinase downstream of LIN-45/Raf and MEK-2/MEK. The M. nematophilum infection study directly supports an ERK/MAPK cascade mediated by MPK-1, and independent LIN-45 genetics place MPK-1 in a predominantly linear Raf-MEK-ERK cascade, so this is a core pathway annotation. Supporting Evidence: PMID:15268855 extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase cascade mediates tail swelling PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0001556 oocyte maturation	IMP PMID:18073423 Multiple functions and dynamic activation of MPK-1 extracell...	KEEP AS NON CORE	Summary: MPK-1 promotes oocyte meiotic maturation and ovulation in the hermaphrodite germline. Reason: The Genetics germline study describes dynamic MPK-1 ERK activation and a role in oocyte meiotic maturation/ovulation, so the annotation is well supported. Oocyte maturation is a germline developmental output of MPK-1 signaling rather than the reusable kinase activity itself. Supporting Evidence: PMID:18073423 MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: The InterPro serine/threonine kinase active-site signature correctly infers protein kinase activity for MPK-1. Reason: MPK-1 carries the conserved MAPK/ERK catalytic domain and its protein kinase activity is directly supported by SKN-1 and NOS-3 phosphorylation evidence. GO:0004672 is broad but true for the MPK-1 kinase core. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference of protein serine/threonine kinase activity is appropriate for MPK-1. Reason: The IBA is placed on a deeply conserved MAPK-family node and includes MPK-1 among the descendants. MPK-1 phosphorylates serine/threonine targets and shows no evidence of kinase-domain loss, so this is a core molecular function. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites
GO:0004674 protein serine/threonine kinase activity	IDA PMID:20624915 The ERK-MAPK pathway regulates longevity through SKN-1 and i...	ACCEPT	Summary: MPK-1 protein serine/threonine kinase activity is supported by direct ERK-dependent substrate phosphorylation. Reason: MPK-1 phosphorylates the transcription factor SKN-1 at sites required for SKN-1 nuclear accumulation and longevity signaling, directly supporting the serine/threonine protein kinase molecular function. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites
GO:0004674 protein serine/threonine kinase activity	IMP PMID:21571224 MPK-1 ERK controls membrane organization in C. elegans oogen...	ACCEPT	Summary: MPK-1 serine/threonine kinase activity drives phosphorylation-dependent NOS-3 regulation during oogenesis. Reason: The full-text oogenesis study shows MPK-1-dependent NOS-3 phosphorylation and uses mpk-1 loss-of-function genetics to connect the kinase to membrane organization during oogenesis. This supports the same core serine/threonine kinase activity assayed in a specific germline context. Supporting Evidence: PMID:21571224 MPK-1 promotes membrane organization by phosphorylation and inactivation of NOS-3
GO:0004707 MAP kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated MAPK/ERK family signatures correctly identify MPK-1 as a MAP kinase. Reason: MPK-1 is the C. elegans ERK homolog and is annotated by reviewed UniProt with EC 2.7.11.24. Experimental work supports its terminal ERK role and substrate phosphorylation activity, matching the IEA to MAP kinase activity. Supporting Evidence: PMID:20624915 mpk-1/ERK1/2
GO:0005515 protein binding	IPI PMID:14704431 A map of the interactome network of the metazoan C. elegans.	REMOVE	Summary: The large-scale yeast two-hybrid study supports a physical interaction dataset, but generic protein binding is not informative for MPK-1. Reason: This IntAct row reports MPK-1 binding to GLA-3 from a high-throughput interactome map. GO:0005515 does not distinguish docking, substrate binding, or another functional kinase interaction; without a specific activity supported by the paper, the generic binding annotation should not be retained. Supporting Evidence: PMID:14704431 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens
GO:0005515 protein binding	IPI PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans...	REMOVE	Summary: The expanded WI-2007/WI8 interactome is good physical-interaction evidence but not a specific MPK-1 molecular function. Reason: The row is another generic MPK-1 to GLA-3 protein-binding assertion from an interactome dataset. Per current curation practice, GO:0005515 should be removed unless it can be replaced by an evidence-backed molecular function that says what the interaction does. Supporting Evidence: PMID:19123269 highly specific high-throughput yeast two-hybrid system
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding is an expected active-site function of the MPK-1 MAP kinase domain. Reason: The InterPro nucleotide-binding and protein-kinase signatures identify the ATP-dependent kinase fold, and the reviewed UniProt catalytic reaction for MPK-1 uses ATP as the phosphoryl donor. ATP binding is therefore part of the core kinase mechanism. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Nuclear activity is conserved among ERK/MAPK-family proteins and is consistent with MPK-1 localization in germline oocytes. Reason: PAINT places nuclear activity at a MAPK-family node that contains MPK-1, and MPK-1 is experimentally observed in the nucleus as well as the cytoplasm during C. elegans germline development. This is a valid active compartment for the kinase. Supporting Evidence: PMID:18073423 MPK-1 activation is temporally/spatially dynamic
GO:0005634 nucleus	IDA PMID:18073423 Multiple functions and dynamic activation of MPK-1 extracell...	ACCEPT	Summary: MPK-1 is experimentally detected in oocyte nuclei during germline development. Reason: The MPK-1 germline study analyzed the spatially dynamic activation of MPK-1 in the gonad and supports nuclear as well as cytoplasmic localization in developing oocytes. Supporting Evidence: PMID:18073423 MPK-1 activation is temporally/spatially dynamic
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasmic MPK-1 activity is conserved across MAPK-family kinases. Reason: The IBA is placed on a broad MAPK node that includes MPK-1, and ERK kinases signal in the cytoplasm before acting on cytosolic and nuclear substrates. C. elegans germline localization also supports MPK-1 in the cytoplasmic compartment. Supporting Evidence: PMID:18073423 MPK-1 activation is temporally/spatially dynamic
GO:0005737 cytoplasm	IDA PMID:18073423 Multiple functions and dynamic activation of MPK-1 extracell...	ACCEPT	Summary: MPK-1 is experimentally detected in the cytoplasm during germline development. Reason: The Lee et al. analysis of MPK-1 ERK activation in the germline supports cytoplasmic localization of activated MPK-1 in oogenic cells, consistent with the expected compartment for ERK substrate phosphorylation. Supporting Evidence: PMID:18073423 MPK-1 activation is temporally/spatially dynamic
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: ARBA cytoplasm prediction is consistent with MPK-1 ERK biology and direct localization evidence. Reason: Although this is an automatic localization row, it agrees with the phylogenetic IBA and with the germline study reporting spatially dynamic MPK-1 activation in the cytoplasmic oogenesis production line. Supporting Evidence: PMID:18073423 MPK-1 activation is temporally/spatially dynamic
GO:0007166 cell surface receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: MAPK/ERK proteins are conserved transducers downstream of cell-surface receptor inputs. Reason: This PAINT inference captures the conserved placement of ERK-family kinases downstream of receptor-coupled Ras/Raf/MEK signaling. MPK-1 is the C. elegans ERK used in receptor tyrosine kinase and other cell-surface signaling contexts, including vulval induction by LET-60/Ras. Supporting Evidence: PMID:8299936 plays an important functional role as an activator in ras-mediated cell signaling in vivo
GO:0007265 Ras protein signal transduction	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	ACCEPT	Summary: MPK-1 is part of the Ras-Raf-MEK-ERK module downstream of LET-60/Ras. Reason: LIN-45/Raf is the Ras effector upstream of MEK-2 and MPK-1, and lin-45 null alleles phenocopy mpk-1 null alleles. Ras protein signal transduction is therefore a direct core pathway context for MPK-1. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP PMID:21673654 EGF signalling activates the ubiquitin proteasome system to ...	KEEP AS NON CORE	Summary: EGF/Ras/MAPK signaling increases UPS activity in adults, placing MPK-1 upstream of this proteostasis output. Reason: The abstract supports regulation of ubiquitin-proteasome system gene expression and activity by EGF signaling through the Ras-MAPK pathway. This is a real adult proteostasis output of MPK-1 signaling but is downstream of the kinase's core MAPK activity. Supporting Evidence: PMID:21673654 EGF signalling upregulates the expression of genes involved in the ubiquitin proteasome system
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: Intracellular signal transduction is a correct parent process for the conserved MPK-1 MAP kinase. Reason: PAINT places this broad signaling term on the same conserved MAPK-family node that carries direct kinase activity and cytoplasmic/nuclear locations. The term is generic but accurately describes MPK-1's role in transmitting intracellular phosphorylation signals. Supporting Evidence: PMID:20624915 The ERK (MPK-1) cascade-mediated life span extension requires SKN-1
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: The LIN-45/Raf genetic interaction supports MPK-1 in vulval induction. Reason: LIN-45/Raf is downstream of LET-60/Ras and upstream of MPK-1 during vulval fate induction. Vulval development is the canonical C. elegans RTK/Ras/MAPK output, but it is retained as a non-core developmental context rather than a core kinase activity. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: MPK-1 contributes to vulval induction through the Ras/MAPK network. Reason: The original IGI source supports a Raf/MEK/ERK pathway in which MPK-1 functions downstream of LET-60/Ras. The individual WormBase interaction partner is preserved from GOA, and the developmental term should be kept as a non-core pathway output. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: Genetic-interaction curation places MPK-1 in the vulval-development Ras/MAPK pathway. Reason: The LIN-45 study establishes a predominantly linear LET-60/Ras-to-MPK-1 ERK relay required for vulval cell fate induction. This row is biologically sound but describes a tissue-specific developmental output. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: Multiple WormBase genetic interactions support MPK-1 activity in Ras-mediated vulval development. Reason: These IGI partners point to the same experimentally supported vulval fate pathway centered on LET-60/Ras, LIN-45/Raf, MEK-2, and MPK-1. The downstream developmental assertion should be kept as non-core. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0040025 vulval development	IMP PMID:8299935 Suppression of activated Let-60 ras protein defines a role o...	KEEP AS NON CORE	Summary: sur-1/mpk-1 was cloned genetically as a downstream LET-60/Ras component needed for vulval differentiation. Reason: Wu and Han identified reduction-of-function sur-1 mutations as suppressors of activated let-60 ras and placed SUR-1/MPK-1 downstream of let-60 in the vulval pathway. Vulval development is a strongly supported but non-core organismal output. Supporting Evidence: PMID:8299935 Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1
GO:0040025 vulval development	IMP PMID:8299936 A MAP kinase homolog, mpk-1, is involved in ras-mediated ind...	KEEP AS NON CORE	Summary: mpk-1 acts cell-autonomously in vulval precursor cells to promote Ras-mediated vulval fates. Reason: Lackner et al. independently cloned mpk-1 and showed that an mpk-1 allele suppresses activated let-60 ras, placing the MAP kinase in Ras-mediated vulval induction. This should be retained as a non-core developmental output of MPK-1 signaling. Supporting Evidence: PMID:8299936 mpk-1 acts cell autonomously in the Pn.p cells
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:27525822 The Invertebrate Lysozyme Effector ILYS-3 Is Systemically Ac...	KEEP AS NON CORE	Summary: MPK-1 activity is required for pathogen-induced ilys-3 transcriptional activation. Reason: The full-text ILYS-3 study found that mpk-1 mutants fail to induce the ilys-3 transcriptional reporter in the gut after M. nematophilum exposure. This supports the row as a non-core transcriptional output of ERK signaling during epithelial defense. Supporting Evidence: PMID:27525822 induction of ilys-3 in the intestine of mpk-1(ku1) mutants exposed to M. nematophilum was severely compromised
GO:0050830 defense response to Gram-positive bacterium	IGI PMID:20617181 Distinct pathogenesis and host responses during infection of...	KEEP AS NON CORE	Summary: MPK-1 contributes genetically to the C. elegans anal-region response to the Gram-positive pathogen S. aureus. Reason: The S. aureus infection study reports that the deformed anal region response to live S. aureus depends on mpk-1/ERK. The evidence supports a defensive Gram-positive infection context, while defense response remains a downstream physiological output of MPK-1 signaling. Supporting Evidence: PMID:20617181 mpk-1/extracellular signal regulated kinase (ERK)
GO:0050830 defense response to Gram-positive bacterium	IMP PMID:15268855 The ERK MAP kinase cascade mediates tail swelling and a prot...	KEEP AS NON CORE	Summary: The MPK-1 ERK cascade mediates a protective swelling response to M. nematophilum infection. Reason: M. nematophilum is a Gram-positive rectal pathogen of C. elegans, and Nicholas and Hodgkin showed that the ERK MAPK cascade protects infected animals from severe constipation by mediating tail swelling. This is a valid host-defense output and non-core relative to the kinase activity. Supporting Evidence: PMID:15268855 protects C. elegans from severe constipation
GO:0106310 protein serine kinase activity	EXP PMID:20624915 The ERK-MAPK pathway regulates longevity through SKN-1 and i...	ACCEPT	Summary: UniProt's serine-kinase assertion is grounded in MPK-1 phosphorylation of SKN-1. Reason: The Okuyama et al. study provides experimental evidence that MPK-1 phosphorylates SKN-1 at sites required for nuclear accumulation. That directly supports serine kinase activity and the associated Rhea reaction. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: The Rhea serine-phosphorylation mapping is appropriate for MPK-1. Reason: RHEA:17989 represents ATP-dependent phosphorylation of a protein serine residue, which is part of the experimentally supported catalytic repertoire of this serine/threonine MAP kinase. Supporting Evidence: PMID:20624915 MPK-1 phosphorylates SKN-1 on the key sites

Gene Description

Existing Annotations Review

Core Functions

MPK-1 is the ATP-dependent ERK/MAP kinase in the C. elegans Ras-Raf-MEK-ERK cascade. It phosphorylates serine/threonine protein substrates to transmit signals from upstream receptor and Ras pathway inputs into cytoplasmic and nuclear outputs.

References

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Notes

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