WormMine: Gene WBGene00002299

• WormBase Gene ID: WBGene00002299
• Gene Name: let-23
• Sequence Name: ZK1067.1
• Brief Description: let-23 encodes an EGF-receptor-family transmembrane tyrosine kinase that affects viability, inductive signaling during development of the vulva, male spicule formation, posterior development of the epidermis, ovulation and stress induced sleep; let-23 is genetically upstream of the let-60/RAS pathway with respect to viability and vulval development, is upstream of phosopholipase C gamma with respect to fertility and sleep, and is expressed in vulval precursor cells and the ALA neuron.
• Organism: Caenorhabditis elegans
• Automated Description: Enables epidermal growth factor receptor activity; lipid binding activity; and molecular function activator activity. Involved in several processes, including determination of adult lifespan; positive regulation of vulval development; and reproductive structure development. Located in cell-cell junction and plasma membrane. Expressed in several structures, including apoptotic cell; egg-laying apparatus; excretory duct cell; head; and vulval precursor cell. Human ortholog(s) of this gene implicated in several diseases, including carcinoma (multiple); hypertension (multiple); and reproductive organ cancer (multiple). Is an ortholog of human EGFR (epidermal growth factor receptor) and ERBB4 (erb-b2 receptor tyrosine kinase 4).
• Biotype: SO:0001217
• Genetic Position: II :1.09455 ±0.000258
• Length (nt): 9702

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00002299

Genomics

4 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:ZK1067.1d.1	ZK1067.1d.1	4287	II: 9197512-9207211
Transcript:ZK1067.1c.1	ZK1067.1c.1	4262	II: 9197518-9207213
Transcript:ZK1067.1a.1	ZK1067.1a.1	4336	II: 9198257-9207213
Transcript:ZK1067.1b.1	ZK1067.1b.1	3789	II: 9199189-9206938

Other

4 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:ZK1067.1d	ZK1067.1d	4008	II: 9197518-9197647
CDS:ZK1067.1b	ZK1067.1b	3789	II: 9199189-9199347
CDS:ZK1067.1a	ZK1067.1a	3972	II: 9198346-9198460
CDS:ZK1067.1c	ZK1067.1c	3987	II: 9197518-9197647

9 RNAi Result

• WBRNAi00059089
• WBRNAi00021795
• WBRNAi00078911
• WBRNAi00078912
• WBRNAi00111705
• WBRNAi00086137
• WBRNAi00069418
• WBRNAi00084770
• WBRNAi00110660

152 Allele

• gk963801
• gk963053
• gk962682
• gk962798
• sa62
• sy1
• sy5
• sy10
• sy12
• sy14
• sy15
• sy16
• sy17
• sy97
• sy278
• WBVar01696100
• WBVar01696101
• WBVar01604419
• sy608
• sy621
• h4646
• sy264
• sy265
• sy220
• sy266
• sy7
• WBVar01826612
• WBVar01826613
• gk942054
• gk942052

1 Chromosome

• WormBase ID: II
• Organism: Caenorhabditis elegans
• Length (nt): 15279421

1 Chromosome Location

• Feature . Primary Identifier: WBGene00002299
• Start: 9197512
• End: 9207213
• Strand: 1

4 Data Sets

• WormBaseAcedbConverter
• GO Annotation data set
• C. elegans genomic annotations (GFF3 Gene)
• Panther orthologue and paralogue predictions

1 Downstream Intergenic Region

• WormBase ID: intergenic_region_chrII_9207214..9210375
• Length (nt): 3162
• Chromosome Location: II: 9207214-9210375
• Organism: Caenorhabditis elegans

142 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts of coding genes that showed significantly decreased expression in muscle.	DESeq2 (version 1.24.0). Transcripts with a false-discovery rate adjusted p-value less than 0.05 were considered significantly differentially expressed.	WBPaper00062325:muscle_depleted_coding-RNA
	Transcripts expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_Food
	Transcripts that showed significantly increased expression in csr-1a(tor159) comparing to in N2 at 25C.	DESeq2, fold change > 2, p-value < 0.05.	WBPaper00061753:csr-1(tor159)_upregulated_25C
	Transcripts that showed significantly increased expression glp-1(e2141); TU3401 animals comparing to in TU3401 animals.	Fold change > 2, FDR < 0.01.	WBPaper00065993:glp-1(e2141)_upregulated
Bacteria infection: Enterococcus faecalis	Genes with increased expression after 24 hours of infection by E.faecalis Fold changes shown are pathogen vs OP50.	For RNA-seq and tiling arrays, log2 fold changes between gene expression values of infected versus uninfected nematodes were calculated. For log2 fold changes > 0.00001 the values > 81.25th percentile were defined as up-regulated and for log2 fold changes < -0.00001 the values < 18.75th percentile were defined as down-regulated.	WBPaper00038438:E.faecalis_24hr_upregulated_TilingArray
	Transcripts expressed in intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Genes with expression level regulated by genotype (N2 vs CB4856) and age at old adults stage (214 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_age_regulated_aging
	Transcripts expressed in seam cells, according to PAT-Seq analysis using Pgrd-10-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:seam_expressed
	Transcripts that showed significantly increased expression in day 1 adult hermaphrodite comparing to in L4 larva fem-3(q20) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-1-adult_vs_L4_upregulated_fem-3(q20)
	Transcripts that showed significantly increased expression in day 1 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-1-adult_vs_L4_upregulated_glp-1(e2141)
	Transcripts that showed significantly increased expression in rrf-3(pk1426) comparing to in N2 at embryo stage.	DESeq2v 1.18.1, fold change > 1.5, adjusted p-value < 0.01.	WBPaper00056169:rrf-3(pk1426)_upregulated_embryo
	Transcripts that showed significantly increased expression after four-day-old young adult worms were placed on NGM plates seeded with OP50 in the presence 5% Agaro-oligosaccharides(AGO) for 24 h, comparing to animals grown in the absence of AGO.	Fold change > 2.	WBPaper00064306:Agaro-oligosaccharides_upregulated
	Transcripts that showed significantly increased expression in sin-3(tm1276) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:sin-3(tm1276)_upregulated
Dietary restriction	Transcripts that showed significantly decreased expression after N2 animals were under dietary restriction (DR, OP50 OD = 0.1) from 3-day post L4 till 6-day post L4 adult hermaphrodite stage, comparing to under ad libtum (AL, OP50 OD = 3) condition.	Bioconductor package edgeR, p < 0.05.	WBPaper00056443:DietaryRestriction_downregulated
Bacteria infection: Staphylococcus aureus MW2. 4 hours of exposure.	Transcripts that showed significantly increased expression after N2 animals had 4 hours of infection by Staphylococcus aureus (MW2).	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:S.aureus-4h_upregulated_N2
	Transcripts that showed significantly decreased expression in N2 animals exposed to 0.1mM Paraquat from hatching to reaching adult stage.	DESeq2 version 1.22.2, p < 0.05	WBPaper00064716:paraquat_downregulated
	Top 300 transcripts enriched in excretory duct, excretory pore according to single cell RNAseq.	Top 300 enriched transcripts were determined by log2.ratio of the tpm in the cell type vs the tpm in the other cells * the log2 of the cell.type tpm.	WBPaper00061340:Excretory_duct_and_pore
	Transcripts that showed significantly decreased expression in sin-3(tm1276) comparing to in N2 at early embryo when there were only 3 -5 eggs in the adult.	DESeq2, fold change > 2, adjusted p-value < 0.01	WBPaper00058598:sin-3(tm1276)_downregulated
	Transcripts depleted in purified oocyte P bodies comparing to in whole oocytes.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00065975:P-body_vs_oocyte_depleted
	Transcripts depleted in purified oocyte P bodies comparing to in the whole animal.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00065975:P-body_vs_WholeAnimal_depleted
	Transcripts that showed significantly increased expression in xrep-4(lax137).	DESeq2. Genes were selected if their p value < 0.01.	WBPaper00066062:xrep-4(lax137)_upregulated
	Genes that showed expression levels higher than the corresponding reference sample (L3/L4 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:dopaminergic-neurons_L3-L4-larva_expressed
	Genes that showed expression levels higher than the corresponding reference sample (L2 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:GABAergic-motor-neurons_L2-larva_expressed
	Transcripts that showed significantly altered expression at URX, AQR, and PQR neurons in camt-1(ok515) animals comparing to in wild type AX1888-1 strain.	RNA-seq data were mapped using PRAGUI - a Python 3-based pipeline for RNA-seq data analysis.	WBPaper00061902:camt-1(ok515)_regulated_URX-AQR-PQR
	Genes that showed expression levels higher than the corresponding reference sample (L2 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:intestine_L2-larva_expressed
	Transcripts that showed significantly increased expression in hda-2(ok1479) comparing to in N2 animals.	DESeq2 (version 1.28.1), FDR < 0.01, fold change > 2.	WBPaper00062159:hda-2(ok1479)_upregulated
	Transcripts that showed significantly increased expression in dpy-21(e428) comparing to in N2 during L3 stage.	DESeq v1.6.3. Fold change > 1.5.	WBPaper00050370:dpy-21(e428)_L3_upregulated
	Transcripts that showed significantly decreased expression after animals were treated with 50uM Rifampicin and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin-Allantoin_downregulated
	Transcripts detected in germline isolated from day-1 adult hermaphrodite animals.	All three experiments have CPM >= 1.	WBPaper00067147:germline_expressed

18 Expression Patterns

• Primary Identifier: Expr1031347
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr1162519
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr15965
• Pattern: Endogenously tagged LIN-2, LIN-7, LIN-10 and LET-23 EGFRallow for the analysis of their localization and expression patterns in other tissues. We found that all four proteins are expressed inneurons and sensory tissue in the head, and along the ventral anddorsal nerve chords. The intestine is prone to a highdegree of autofluorescence and was excluded from the initialanalysis. Whereas LET-23 EGFR and LIN-7 overlapped minimallyin the head, LIN-2 and LIN-7 colocalized strongly in theneural ring, and the ventral and dorsal nerve chords. Ofnote, we observed that LIN-2 was more strongly expressed in theisthmus of the pharynx than LIN-7. In contrast, LIN-7 wasmore strongly expressed in the gonad and uterus than LIN-2. LIN-10 overlapped minimally with LIN-2 in the neural ring and nerve chords, and shared very little overlap with LET-23 EGFR in other neural tissues in the head of the worm. LET-23::mK2 was strongly expressed in the excretory duct cell in which it signals through the LET-60 Ras/MPK-1 ERK pathway to regulate excretory duct cell development (Abdus-Saboor et al., 2011; Yochem et al., 1997).

• Primary Identifier: Expr9316
• Pattern: In wild type, a let-23:LET-23-GFP translational reporter is expressed in several non-neuronal cells and a small number of neurons, including ALA.

• Primary Identifier: Expr9114
• Remark: Picture: Fig 3A.
• Pattern: Both methods revealed LET-23 expression in the ALA neuron, identified by the position of its cell body in the dorsal ganglion and its two lateral axonal projections, in two ventral head neurons that send projections into the nerve ring, and in a single tail neuron. LET-23 was also expressed in the pharyngeal-intestinal valve as well as in six cells anterior to the first pharyngeal bulb that project to a ring around the buccal cavity and are likely to be to the posterior arcade epithelial cells.

• Primary Identifier: Expr9353
• Pattern: LET-23 expression can be observed in hypodermal cells throughout the development and in intestinal cells when animals mature into adulthood.

• Primary Identifier: Expr13450
• Pattern: LET-23::GFP is expressed in the presumptive duct and G1 pore at ventral enclosure and in the duct (bracket) at 3-fold.

• Primary Identifier: Expr11935
• Pattern: let-23 is expressed in dying cells. Notably, the GFP signal was observed in the ABpl/rpppapp corpses.

• Primary Identifier: Expr11776
• Subcellular Localization: LET-23::GFP is localized at basolateral and apical plasma membrane of the vulval cells in wild-type larvae.

• Primary Identifier: Expr15966
• Subcellular Localization: LET-23::mK2 localized to the basolateral and apical membrane domains of the VPCs, as has been described previously for endogenous LET-23 EGFRand other LET-23 EGFR reporters (Haag et al., 2014; Skorobogataet al., 2014; Whitfield et al., 1999). We found that LET-23::mK2 and mNG::LIN-7 overlapped at thebasolateral plasma membrane in L3 larvae (from P6.p to P6.pxx). This overlap was more apparent in the differentiated vulval cells (L4).

• Primary Identifier: Expr1010184
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr688
• Remark: This information was extracted from published material (Archana Sharma-Oates, Andrew Mounsey and Ian A. Hope).
• Pattern: let-23 expression is first observed in the early L3 larvae (1-3 h after L2 molt, 1.5-3.5 h before division of the Pn.p cells), in all six Pn.p cells and is concentrated in a lateral ring. let-23 appears to be specifically associated with the cell junction. Let-23 expression decreases rapidly in the 2o cells (P5.p and P7.p) starting at 3 h and disappearing completely by 3.5 h after L2 molt. Expression in P3.p, P4.p and P8.p decreases gradually until no longer seen 3.5-4 h after L2 molt. Expression in P6.p increases starting at 4-4.5 h after L2 molt. At this stage expression is observed in a lateral ring in the plasma membrane. At approximately 4-4.5 h after the L2 molt, expression is localized to the P6.p cell junction in 69% of the animals and staining is more punctate. In the remaining 31% of animals staining is broadly distributed on the apical plasma membrane of P6.p.
• Subcellular Localization: let-23 specifically associate with cell junctions.

• Primary Identifier: Expr1281
• Pattern: In wild-type larvae, LET-23 RTK is first expressed in the vulval precursor cells in the early L2 stage. LET-23 staining is observed throughout the basolateral membrane of all six vulval precursor cells. In five of the vulval precursor cells (P3.p, P4.p, P5.p, P7.p, and P8.p), little or no LET-23 is present in the apical membrane domain. In the remaining vulval precursor cell (P6.p), LET-23 is present in both the basolateral and apical membrane domains. As P6.p divides in early L3, LET-23 staining continues to be present in both the basolateral and apical membrane domains.
• Subcellular Localization: Appears on both the basolateral and apical membrane domains, with higher levels in the apical membrane domain.

• Primary Identifier: Expr2013050
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr15705
• Pattern: In late L2/early L3 larvae before the VPCs have started dividing, a translational LET-23::GFP reporter was up-regulated in the 1 ̊ VPC P6.p, while expression faded in the other, more distal VPCs. Most of the LET-23:: GFP protein in P6.p was detected, approximately at equal levels, on the basolateral and apical plasma membranes. Only a faint and diffuse intracellular LET-23::GFP signal could be observed in the VPCs of wild-type animals. After the first round of VPC divisions, LET-23::GFP continued to be strongly expressed on the plasma membrane of the 1 ̊ P6.p descendants.

• Primary Identifier: Expr15706
• Pattern: In late L2/early L3 larvae before the VPCs have started dividing, a translational LET-23::GFP reporter was up-regulated in the 1 ̊ VPC P6.p, while expression faded in the other, more distal VPCs. Most of the LET-23:: GFP protein in P6.p was detected, approximately at equal levels, on the basolateral and apical plasma membranes. Only a faint and diffuse intracellular LET-23::GFP signal could be observed in the VPCs of wild-type animals. After the first round of VPC divisions, LET-23::GFP continued to be strongly expressed on the plasma membrane of the 1 ̊ P6.p descendants.

• Primary Identifier: Expr2265
• Pattern: Expression of let-23::GFP was detected in the uv1 cells.

• Primary Identifier: Expr2031282
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

42 GO Annotation

17 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00002299
• Start: 9197512
• End: 9207213
• Strand: 1

42 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 9702

1 Sequence Ontology Term

• Name: gene

21 Strains

• WBStrain00022495
• WBStrain00026931
• WBStrain00027026
• WBStrain00030958
• WBStrain00030929
• WBStrain00030811
• WBStrain00030810
• WBStrain00030821
• WBStrain00030820
• WBStrain00030836
• WBStrain00030835
• WBStrain00030837
• WBStrain00030848
• WBStrain00030842
• WBStrain00030807
• WBStrain00030806
• WBStrain00030808
• WBStrain00030721
• WBStrain00033485
• WBStrain00034220
• WBStrain00047173

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrII_9194296..9197511
• Length (nt): 3216
• Chromosome Location: II: 9194296-9197511
• Organism: Caenorhabditis elegans