lin-45

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: LIN-45 participates in the ERK-type MAPK cascade during the response to rectal infection. Reason: The same LIN-45/MEK-2/MPK-1 ERK cassette that patterns the vulva is also used downstream of Microbacterium nematophilum infection, so the broad MAPK cascade annotation is a correct core pathway assertion for this RAF. Supporting Evidence: PMID:15268855 an extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase cascade mediates tail swelling
GO:0001708 cell fate specification	IMP PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: lin-45 loss-of-function alleles impair vulval precursor cell fate induction. Reason: Cell-fate specification during vulval induction is a direct developmental output of LET-60/LIN-45/MEK-2/MPK-1 signaling, but it is context-specific rather than the reusable RAF kinase activity itself. Supporting Evidence: PMID:11861555 lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates
GO:0002119 nematode larval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: LIN-45 function with LET-60/Ras contributes to larval viability. Reason: The LET-60/Ras interaction supports LIN-45 acting in the developmental Ras-Raf-MEK-ERK cassette; nematode larval development is a real organismal output of that signaling but is not LIN-45's core molecular function. Supporting Evidence: PMID:11861555 The phenotype caused by the most severe mutations demonstrates that lin-45 is essential for larval viability
GO:0002119 nematode larval development	IMP PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: Severe lin-45 alleles show that RAF signaling is required for larval viability. Reason: Larval lethality from lin-45 loss establishes an in vivo developmental requirement for the Ras-Raf-MEK-ERK cassette. The process is kept as a non-core phenotype-level consequence of losing the core LIN-45 kinase. Supporting Evidence: PMID:11861555 Weak, intermediate, and strong loss-of-function or null mutations were isolated.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: The InterPro kinase-domain mapping is true but too broad for LIN-45. Reason: LIN-45 is not just any protein kinase; it is the RAF MAP kinase kinase kinase upstream of MEK-2 and MPK-1, so the generic protein kinase term should be replaced by GO:0004709. Proposed replacements: MAP kinase kinase kinase activity Supporting Evidence: file:worm/lin-45/lin-45-uniprot.txt DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000003	MODIFY	Summary: EC:2.7.11.1 captures the serine/threonine kinase chemistry but not the specific RAF role. Reason: LIN-45 is a serine/threonine protein kinase whose curated molecular function is MAP kinase kinase kinase activity in the ERK module; GO:0004709 is therefore a more informative replacement. Proposed replacements: MAP kinase kinase kinase activity Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0004709 MAP kinase kinase kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT places LIN-45 in the conserved RAF family MAPKKK clade. Reason: MAP kinase kinase kinase activity is the defining catalytic function of RAF proteins, and the IBA placement is consistent with C. elegans genetic evidence that LIN-45 acts upstream of MEK-2 and MPK-1 in a linear ERK MAPK pathway. Supporting Evidence: PMID:11861555 Raf functions in signal transmission by phosphorylating and activating a mitogen-activated protein (MAP) kinase kinase named MEK
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: LIN-45 has the conserved protein-kinase ATP-binding machinery. Reason: ATP binding is required for the catalytic cycle of LIN-45's RAF kinase domain and is supported by conserved protein kinase domain signatures in the reviewed UniProtKB record. Supporting Evidence: file:worm/lin-45/lin-45-uniprot.txt DR InterPro; IPR017441; Protein_kinase_ATP_BS.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: PAINT infers cytoplasmic activity for the conserved RAF kinase family. Reason: RAF proteins are cytoplasmic signaling kinases that are recruited into Ras/MAPK signaling complexes, and there is no target-specific evidence here suggesting C. elegans LIN-45 has diverged from that conserved localization.
GO:0007165 signal transduction	IEA GO_REF:0000120	MODIFY	Summary: The automated signal-transduction call is correct in spirit but too broad for LIN-45. Reason: The InterPro Ras-binding-domain hit points to RAF function in Ras-dependent ERK signaling, so the generic signal transduction assertion should be replaced by ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0007265 Ras protein signal transduction	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	ACCEPT	Summary: LET-60/Ras genetically activates LIN-45-dependent RAF signaling. Reason: LIN-45 is the RAF effector downstream of LET-60/Ras in the core vulval induction cascade, so Ras protein signal transduction is an appropriate pathway-level assertion. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras
GO:0031267 small GTPase binding	IPI PMID:9674433 SUR-8, a conserved Ras-binding protein with leucine-rich rep...	ACCEPT	Summary: LIN-45 binds the C. elegans LET-60/Ras small GTPase. Reason: The original IPI row records a LET-60 interaction with LIN-45. Although the cached PMID:9674433 abstract centers on SUR-8, the assertion is consistent with the LIN-45 Ras-binding domain, whose missense alleles impair full RAF function in vivo. Supporting Evidence: PMID:11861555 three missense mutations that affect the Ras-binding domain
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: LIN-45 and LET-60/Ras act together in vulval induction. Reason: Vulval development is the classic C. elegans output of the LET-60/LIN-45/MEK-2/MPK-1 cascade. The annotation is correct, but the developmental process is a tissue-specific output of the RAF kinase. Supporting Evidence: PMID:11861555 lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: LIN-45 genetically participates in vulval development. Reason: The interaction evidence supports the same vulval Ras-Raf-MEK-ERK cassette. Keep the process annotation as a well supported developmental output rather than the core catalytic function. Supporting Evidence: PMID:11861555 lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: Genetic interactions place LIN-45 in the vulval induction pathway. Reason: LIN-45 acts through the conserved ERK cascade to induce vulval cell fates; vulval development is kept as a specific developmental output of that signaling. 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: LIN-45 genetically participates in vulval development. Reason: The IGI row captures a genuine vulval-development requirement for LIN-45, downstream of LET-60/Ras and upstream of MEK-2/MPK-1; this is a non-core developmental output of the RAF MAPKKK. Supporting Evidence: PMID:11861555 lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates
GO:0040025 vulval development	IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: LIN-45 functions in the Ras-Raf-ERK module that patterns the vulva. Reason: The annotation reflects LIN-45's developmental deployment during vulval induction. It is correct but more context-specific than LIN-45's core MAP kinase kinase 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	IMP PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi...	KEEP AS NON CORE	Summary: Multiple lin-45 alleles disrupt vulval development. Reason: The lin-45 allelic series directly supports a vulval induction role, but vulval development is a tissue-specific developmental output rather than the central RAF molecular activity. Supporting Evidence: PMID:11861555 The lin-45 alleles include three missense mutations that affect the Ras-binding domain
GO:0040025 vulval development	IMP PMID:23154983 SEL-10/Fbw7-dependent negative feedback regulation of LIN-45...	KEEP AS NON CORE	Summary: LIN-45 stability feedback modulates vulval induction. Reason: SEL-10/Fbw7-dependent turnover of LIN-45 tunes Ras-Raf-ERK signaling during vulval induction, supporting the vulval development process while leaving it as a context-specific output of the RAF kinase. Supporting Evidence: PMID:23154983 For functional assessments, we focused on LIN-45, a component of the signal transduction pathway underlying vulval induction
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 LIN-45 ERK cascade contributes to defense against M. nematophilum rectal infection. Reason: LIN-45 executes the ERK MAPK cassette in this infection response, but defense against a Gram-positive pathogen is a physiological deployment of the pathway rather than LIN-45's conserved core activity. Supporting Evidence: PMID:15268855 protects C. elegans from severe constipation
GO:0070371 ERK1 and ERK2 cascade	IBA GO_REF:0000033	ACCEPT	Summary: PAINT infers conserved RAF participation in the ERK cascade. Reason: LIN-45 is the C. elegans RAF in the LET-60/Ras to MEK-2 to MPK-1/ERK module; the ERK cascade term is the appropriately specific conserved process. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MODIFY	Summary: The Rhea serine kinase mapping is true but less specific than LIN-45's RAF MAPKKK activity. Reason: LIN-45 catalyzes phosphorylation within the RAF kinase family, but protein serine kinase activity is broader and less informative than MAP kinase kinase kinase activity. Proposed replacements: MAP kinase kinase kinase activity Supporting Evidence: file:worm/lin-45/lin-45-uniprot.txt CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +

Gene Description

Existing Annotations Review

Core Functions

RAF-family MAP kinase kinase kinase activity that relays LET-60/Ras input to MEK-2 and the MPK-1 ERK MAPK cascade.

References

Deep Research

WormBase

WormBase gene description for lin-45 (worm)

📚 Additional Documentation

Notes

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