let-23

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0002119 nematode larval development	IMP PMID:631558 Crossover suppressors and balanced recessive lethals in Caen...	UNDECIDED	Summary: The GOA row links LET-23 to larval development, but the cached abstract does not expose the let-23-specific experiment. Reason: PMID:631558 is an early LGII balancer/mutagenesis paper and the cached record is abstract-only. Because the visible abstract does not name let-23 or describe the allele-to-phenotype mapping behind this WormBase IMP row, the annotation should be preserved for curator follow-up rather than accepted or removed from incomplete evidence.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: The InterPro kinase-domain inference is sound but too general for LET-23. Reason: LET-23 is an EGFR-family single-pass receptor that catalyzes protein tyrosine phosphorylation in the receptor complex. The broad parent term protein kinase activity should be replaced by the existing, more informative receptor tyrosine kinase term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	MODIFY	Summary: Protein tyrosine kinase activity is correct but less specific than the receptor tyrosine kinase activity already supported for LET-23. Reason: The RHEA/InterPro inference captures the tyrosine kinase chemistry, but LET-23 performs that chemistry as a transmembrane EGFR-family receptor. Use GO:0004714 to retain the catalytic claim at the correct specificity. Proposed replacements: transmembrane receptor protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT receptor-tyrosine-kinase activity transfer matches the inherited LET-23 catalytic role. Reason: LET-23 is the C. elegans EGFR-family receptor and UniProt records EC:2.7.10.1 for transfer of phosphate from ATP to protein tyrosine. The PAINT row is at the right specificity for this conserved kinase-domain activity.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC:2.7.10.1 maps cleanly to LET-23 transmembrane receptor protein tyrosine kinase activity. Reason: The Enzyme Commission mapping captures the same receptor tyrosine-protein kinase chemistry assigned in the reviewed UniProt record for LET-23.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:26060020 Ligand regulation of a constitutively dimeric EGF receptor.	ACCEPT	Summary: Biochemical reconstitution shows that the C. elegans LIN-3 ligand activates LET-23 as an EGFR-family receptor. Reason: Freed and colleagues expressed LET-23 and LIN-3 fragments and showed that LIN-3 binds and allosterically activates a constitutive LET-23 dimer, directly supporting epidermal growth factor receptor activity. Supporting Evidence: PMID:26060020 LET-23 is constitutively dimeric, yet responds to its ligand LIN-3 without changing oligomerization state.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:29358026 Regulation of Kinase Activity in the Caenorhabditis elegans ...	ACCEPT	Summary: LET-23 is experimentally activated by LIN-3 in cells through its EGFR-family kinase-domain mechanism. Reason: Liu and colleagues analyzed the LET-23 kinase domain and full-length receptor and found that interface mutations block LIN-3-dependent signaling, supporting a ligand-regulated EGFR receptor activity. Supporting Evidence: PMID:29358026 these mutations also abrogated LET-23 signaling in cells in response to its ligand, LIN-3.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding is a required cofactor interaction for LET-23 protein tyrosine kinase activity. Reason: LET-23 has a protein kinase catalytic domain and is assigned the RHEA/EC tyrosine kinase reaction that transfers phosphate from ATP to protein tyrosyl residues, so the InterPro ATP-binding annotation is consistent with its kinase mechanism.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: PAINT transfer to plasma membrane matches the normal site of LET-23 receptor signaling. Reason: LET-23 is a single-pass cell-surface EGFR-family receptor, and independent C. elegans imaging papers place LET-23 on apical and basolateral domains of vulval precursor cell plasma membranes.
GO:0005911 cell-cell junction	IDA PMID:8612272 LET-23 receptor localization by the cell junction protein LI...	ACCEPT	Summary: LET-23 localization to vulval precursor-cell junctions was shown by receptor localization assays. Reason: Simske and colleagues found that LET-23 is localized to Pn.p cell junctions by LIN-7 and that this localization is needed for vulval signaling, so cell-cell junction is a direct experimental localization. Supporting Evidence: PMID:8612272 LET-23 is also localized to the cell junctions, and both LIN-2 and LIN-7 are required for this localization.
GO:0006355 regulation of DNA-templated transcription	IMP PMID:21673654 EGF signalling activates the ubiquitin proteasome system to ...	KEEP AS NON CORE	Summary: LET-23/EGF signaling can change adult UPS and chaperone gene expression, but this is a context-specific downstream output. Reason: The cached abstract supports an EGF-to-Ras/MAPK-to-EOR-1/EOR-2 pathway that up-regulates ubiquitin proteasome system genes in adults. That is a defensible LET-23 signaling output, but transcriptional regulation is indirect relative to the receptor kinase activity and EGFR/Ras/MAPK signaling that define LET-23. Supporting Evidence: PMID:21673654 We find that EGF signalling regulates lifespan via the Ras-MAPK pathway and the PLZF transcription factors EOR-1 and EOR-2.
GO:0007173 epidermal growth factor receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT EGFR-pathway transfer is consistent with LET-23 as the sole C. elegans EGFR-family receptor. Reason: LET-23 mediates LIN-3/EGF signaling in vulval induction and other developmental and physiological outputs, and the PAINT row places the receptor in the named EGFR signaling pathway rather than a generic receptor pathway.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:26060020 Ligand regulation of a constitutively dimeric EGF receptor.	ACCEPT	Summary: LIN-3-dependent activation of LET-23 directly supports EGFR signaling. Reason: Biochemical activation of full-length LET-23 by LIN-3 shows that LET-23 is a ligand-regulated nematode EGFR receptor. Supporting Evidence: PMID:26060020 LET-23 activation remains strictly dependent on addition of LIN-3
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:29358026 Regulation of Kinase Activity in the Caenorhabditis elegans ...	ACCEPT	Summary: LET-23 kinase-domain activation is required for LIN-3-dependent EGFR signaling. Reason: Mutations in the allosteric kinase-domain interfaces block LIN-3-induced full-length receptor signaling, so the biochemical work supports LET-23's role in the EGFR pathway. Supporting Evidence: PMID:29358026 these mutations also abrogated LET-23 signaling in cells in response to its ligand, LIN-3.
GO:0007173 epidermal growth factor receptor signaling pathway	ISS PMID:1979659 The let-23 gene necessary for Caenorhabditis elegans vulval ...	ACCEPT	Summary: The human EGFR sequence similarity inference correctly anticipated LET-23 as an EGFR-family receptor in vulval signaling. Reason: Aroian and colleagues cloned let-23 and showed that it encodes an EGFR-subfamily tyrosine kinase upstream of ras in vulval fate determination, validating the EGFR signaling assignment. Supporting Evidence: PMID:1979659 let-23 encodes a putative tyrosine kinase of the epidermal growth factor receptor subfamily.
GO:0008289 lipid binding	IDA PMID:29358026 Regulation of Kinase Activity in the Caenorhabditis elegans ...	ACCEPT	Summary: Vesicle-surface LET-23 kinase assays directly used lipid surfaces to stimulate the kinase domain. Reason: The in vitro kinase work showed that concentrating histidine-tagged LET-23 kinase domain on DOGS-NTA-Ni-containing lipid vesicles activates catalytic activity, supporting lipid binding as an assayed biochemical property in that regulatory setup. Supporting Evidence: PMID:29358026 its activity is significantly increased by concentrating it on the surface of lipid vesicles
GO:0009925 basal plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT basal-plasma-membrane transfer is consistent with LET-23 signaling toward the basal anchor-cell ligand source. Reason: LET-23 localizes to the basolateral membrane of vulval precursor cells, facing the somatic-gonad LIN-3/EGF source. Basal plasma membrane is therefore compatible with the experimentally observed LET-23 signaling compartment.
GO:0016323 basolateral plasma membrane	EXP PMID:10359617 Basolateral localization of the Caenorhabditis elegans epide...	ACCEPT	Summary: Endogenous LET-23 is present on the basolateral membrane of vulval epithelial precursor cells. Reason: Anti-LET-23 staining showed LET-23 throughout the basolateral membrane of vulval precursor cells in wild-type larvae, directly supporting the basolateral plasma membrane annotation. Supporting Evidence: PMID:10359617 LET-23 staining is observed throughout the basolateral membrane of all six vulval precursor cells
GO:0016323 basolateral plasma membrane	EXP PMID:32053105 The CHORD protein CHP-1 regulates EGF receptor trafficking a...	ACCEPT	Summary: A modern LET-23::GFP trafficking study confirms LET-23 delivery to the basolateral vulval precursor-cell surface. Reason: Haag and colleagues used LET-23::GFP to assay EGFR trafficking in C. elegans and explicitly connect basolateral receptor localization with efficient receptor activation by anchor-cell LIN-3. Supporting Evidence: PMID:32053105 The basolateral localization of LET-23 by the tripartite LIN-2/CASK, LIN-10/MINT and LIN-7/VELIS protein complex is necessary for efficient receptor activation
GO:0016323 basolateral plasma membrane	IDA PMID:9753323 The LIN-2/LIN-7/LIN-10 complex mediates basolateral membrane...	ACCEPT	Summary: The LIN-2/LIN-7/LIN-10 paper directly supports basolateral localization of LET-23. Reason: Kaech and colleagues showed that LET-23 is basolateral in polarized vulval epithelial cells and that the LIN-2/LIN-7/LIN-10 complex mediates that localization through direct binding, so the IDA row is well supported. Supporting Evidence: PMID:9753323 In C. elegans, the LET-23 receptor tyrosine kinase is localized to the basolateral membranes of polarized vulval epithelial cells.
GO:0016323 basolateral plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt subcellular-location mapping to basolateral plasma membrane agrees with direct LET-23 imaging. Reason: Basolateral membrane localization is repeatedly observed for LET-23 in vulval precursor cells, and the UniProtKB-SubCell mapping is therefore a conservative electronic restatement of an experimentally supported location.
GO:0016324 apical plasma membrane	EXP PMID:32053105 The CHORD protein CHP-1 regulates EGF receptor trafficking a...	ACCEPT	Summary: LET-23 can be assayed on the apical surface during receptor trafficking and localization experiments. Reason: CHP-1 loss causes LET-23 trafficking defects and Haag and colleagues assayed apical and basolateral LET-23 localization in vulval precursor cells, supporting the apical plasma membrane row. Supporting Evidence: PMID:32053105 Loss of chp-1 causes the retention of the EGFR in the ER and decreases MAPK signaling.
GO:0016324 apical plasma membrane	IDA PMID:10359617 Basolateral localization of the Caenorhabditis elegans epide...	ACCEPT	Summary: Endogenous LET-23 is detectable on the apical plasma membrane at defined vulval precursor-cell stages and positions. Reason: Anti-LET-23 staining showed both basolateral and apical receptor in early L2 cells and in P6.p during vulval induction, directly supporting this localization. Supporting Evidence: PMID:10359617 LET-23 RTK is first expressed in the vulval precursor cells in the early L2 stage and appears on both the basolateral and apical membrane domains
GO:0016324 apical plasma membrane	IDA PMID:8612272 LET-23 receptor localization by the cell junction protein LI...	ACCEPT	Summary: LIN-7-dependent LET-23 localization experiments support an apical plasma-membrane pool when junctional localization fails. Reason: The Simske paper is the source for LET-23 receptor-localization assays in vulval precursor cells; because GOA carries this as an IDA row from WormBase and the cached abstract confirms LET-23 localization at cell junctions by LIN-7, the apical membrane assertion is retained. Supporting Evidence: PMID:8612272 proper localization of LET-23 receptor to the Pn.p cell junctions is required for signaling activity.
GO:0016324 apical plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt apical-cell-membrane mapping is consistent with experimentally observed LET-23 apical pools. Reason: LET-23 is a single-pass plasma-membrane receptor with both apical and basolateral populations in vulval epithelial cells; the electronic UniProtKB-SubCell row is therefore consistent with the reviewed subcellular-location summary.
GO:0016328 lateral plasma membrane	IDA PMID:8612272 LET-23 receptor localization by the cell junction protein LI...	ACCEPT	Summary: LET-23 is junction-proximal on the lateral surface of vulval precursor cells. Reason: Simske and colleagues localized LET-23 to Pn.p cell junctions and showed that LIN-2 and LIN-7 are required for the junctional localization needed for signaling, supporting a lateral plasma-membrane receptor pool. Supporting Evidence: PMID:8612272 LET-23 is also localized to the cell junctions, and both LIN-2 and LIN-7 are required for this localization.
GO:0030182 neuron differentiation	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Neuron differentiation is a plausible EGFR-family output in other animals but is not established for C. elegans LET-23. Reason: The PANTHER node groups receptor tyrosine kinases that can regulate neural development in fly and vertebrate systems, but direct C. elegans LET-23 evidence supports post-developmental ALA-neuron quiescence rather than neuronal differentiation. This IBA appears to over-project a context-specific developmental output onto worm LET-23. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000698827 SUPPORTS SOURCE BUT NOT TARGET The EGFR-family node supports neuron-differentiation biology in some animals, but the cached worm evidence exposes a nondevelopmental neuronal LET-23 role in sleep-like quiescence.
GO:0030431 sleep	IMP PMID:17891142 Epidermal growth factor signaling induces behavioral quiesce...	KEEP AS NON CORE	Summary: LET-23 mediates an EGF-induced behavioral quiescence state in the ALA neuron. Reason: Van Buskirk and Sternberg showed that ectopic LIN-3 uses neuronal LET-23 and PLC-gamma to stop feeding and locomotion, a worm sleep-like state. This is a real physiological LET-23 output but not the receptor's conserved catalytic core. Supporting Evidence: PMID:17891142 These effects are mediated by neuronal EGFR (also called LET-23) and phospholipase C-gamma (PLC-gamma), diacylglycerol-binding proteins, and regulators of synaptic vesicle release.
GO:0030539 male genitalia development	IMP PMID:7607066 The lin-3/let-23 pathway mediates inductive signalling durin...	KEEP AS NON CORE	Summary: The LIN-3/LET-23 pathway mediates inductive signaling during male spicule development. Reason: Reduced function in lin-3, let-23, sem-5, let-60, or lin-45 disrupts anterior spicule cell fates, so male genital development is a valid organismal output of LET-23/Ras/MAPK signaling but not the receptor kinase core. Supporting Evidence: PMID:7607066 Reduction-of-function mutations in lin-3, let-23, sem-5, let-60 or lin-45 disrupt the fate of anterior cells.
GO:0030728 ovulation	IMP PMID:9491893 Inositol trisphosphate mediates a RAS-independent response t...	KEEP AS NON CORE	Summary: LET-23 regulates ovulation through a Ras-independent IP3/Ca2+ signaling branch. Reason: Clandinin and colleagues showed that LET-23 signals through an IP3-receptor effector to control spermathecal dilation and ovulation. This is a direct tissue-specific output of LET-23 but separate from the core Ras/MAPK branch. Supporting Evidence: PMID:9491893 Signals transduced by LET-23 control ovulation through changes in spermathecal dilation
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 signaling increases adult UPS activity downstream of Ras/MAPK-dependent transcriptional regulation. Reason: The phenotype is downstream of the EGF-Ras/MAPK pathway in adult lifespan regulation and is therefore a legitimate but context-specific LET-23 output, not the receptor's primary molecular function. Supporting Evidence: PMID:21673654 EGF signalling upregulates the expression of genes involved in the ubiquitin proteasome system (UPS), including the Skp1-like protein SKR-5
GO:0038127 ERBB signaling pathway	IEA GO_REF:0000117	MODIFY	Summary: The ARBA ERBB-pathway call is directionally correct but broader than the named LET-23 EGFR pathway. Reason: C. elegans has a single EGFR-like receptor, LET-23, and the reviewed experimental and PAINT rows support GO:0007173 epidermal growth factor receptor signaling pathway. That term is more precise than the pan-ERBB pathway term for this nematode receptor. Proposed replacements: epidermal growth factor receptor signaling pathway
GO:0040026 positive regulation of vulval development	IMP PMID:3996896 Identification and characterization of 22 genes that affect ...	KEEP AS NON CORE	Summary: LET-23 is a positive regulator of C. elegans vulval induction. Reason: Classical vulval-lineage genetics identified genes required for the Vulvaless versus Multivulva decision, and later cloning placed let-23 upstream of let-60 ras in this induction pathway. Vulval development is a major organismal output of LET-23 signaling but is downstream of its core receptor kinase activity. Supporting Evidence: PMID:1979659 The let-23 gene is required for induction of the Caenorhabditis elegans vulva.
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Anti-apoptotic signaling is not an established worm LET-23 output. Reason: Mammalian and fly EGFR signaling can feed survival pathways, but the cached C. elegans LET-23 evidence supports vulval induction, male spicule development, ovulation, sleep-like quiescence, and UPS regulation rather than negative regulation of apoptosis. The PAINT transfer likely reflects a lineage- or tissue-specific EGFR-family output. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000698827 SUPPORTS SOURCE BUT NOT TARGET The EGFR-family source node is experimentally grounded for anti-apoptotic signaling in other animals, but this downstream survival phenotype is not exposed in the worm LET-23 evidence.
GO:0043235 signaling receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: PAINT correctly places LET-23 in an EGFR-family signaling receptor complex. Reason: LET-23 signals as an EGFR-family receptor dimer and forms ligand-regulated receptor complexes at the plasma membrane; this cellular component term is appropriate for the inherited receptor-layer role.
GO:0043410 positive regulation of MAPK cascade	IBA GO_REF:0000033	ACCEPT	Summary: LET-23 positively regulates the conserved Ras/MAPK cascade. Reason: Vulval induction, spicule development, and other LET-23 outputs use the Sem-5/Sos-1/LET-60/Ras/LIN-45/Raf/MEK-2/MPK-1 cassette, and the PAINT transfer captures the conserved receptor-to-MAPK direction of regulation.
GO:0050679 positive regulation of epithelial cell proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: LET-23 induces epithelial vulval precursor-cell divisions, but the epithelial-proliferation term is a broad downstream output. Reason: C. elegans LET-23 drives Pn.p/vulval precursor-cell induction and division downstream of LIN-3, so an epithelial proliferation readout is biologically plausible. It is kept as non-core because the more direct worm process is vulval cell fate specification by an EGFR/Ras/MAPK receptor pathway.
GO:0060065 uterus development	IMP PMID:31398431 EGL-38/Pax coordinates development in the Caenhorhabditis el...	KEEP AS NON CORE	Summary: LET-23/EGFR signaling participates in the reciprocal vulva-to-uterus signal that specifies uv1 fate. Reason: The Chasser study shows that let-23/EGFR activity in the egg-laying system is needed for uterine ventral cell placement and EGL-38 reporter expression. That makes uterus development a valid reproductive-system output of LET-23 signaling but not the receptor's core molecular function. Supporting Evidence: PMID:31398431 expression of EGL-38::GFP in the uv1 cells is dependent on let-23/EGFR activity in the egg-laying system.
GO:0072327 vulval cell fate specification	IMP PMID:20230814 A strawberry notch homolog, let-765/nsh-1, positively regula...	KEEP AS NON CORE	Summary: LET-23 is required for EGFR/Ras-dependent vulval precursor-cell fate specification. Reason: let-23 encodes the receptor in the LIN-3/EGF to Ras pathway that patterns vulval precursor cells. Vulval fate specification is a major developmental output of LET-23, but it is one tissue context downstream of the receptor kinase and EGFR pathway. Supporting Evidence: PMID:1979659 let-23 acts upstream of let-60 ras in the vulval determination pathway
GO:0140677 molecular function activator activity	IDA PMID:29358026 Regulation of Kinase Activity in the Caenorhabditis elegans ...	ACCEPT	Summary: LET-23 kinase domains allosterically activate one another in the receptor dimer. Reason: The allosteric-activator role is intrinsic to HER/EGFR-family kinase dimers: one kinase domain serves as activator for the partner receiver. Liu and colleagues showed that LET-23 uses the same broad asymmetric-dimer logic for ligand-dependent signaling. Supporting Evidence: PMID:29358026 mutations within the putative allosteric dimer interface abrogate activity of the isolated LET-23 kinase and of the full-length receptor

Gene Description

Existing Annotations Review

Core Functions

LIN-3-activated EGFR receptor tyrosine kinase activity at epithelial plasma membranes that initiates LET-23/Ras/MAPK signaling.

References

Deep Research

WormBase

WormBase gene description for let-23 (worm)

📚 Additional Documentation

Notes

let-23 notes

2026-09-30 annotation review

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