WormMine: Gene WBGene00003031

• WormBase Gene ID: WBGene00003031
• Gene Name: lin-46
• Sequence Name: R186.4
• Brief Description: lin-46 encodes one of two C. elegans paralogs of bacterial MoeA proteins and mammalian gephyrins (E domain, only); LIN-46 is predicted to function as a scaffolding protein for a developmental timing complex, and may also play a role in molybdenum cofactor biosynthesis; identified in screens for suppressors of precocious heterochronic mutations in lin-14 and lin-28, lin-46 is required for stage-specific developmental events at the third larval and adult stages of development; as a component of the heterochronic pathway, lin-46 appears to act immediately downstream of lin-28, which encodes a pre-miRNA binding protein required for cell fate specification at the L2 stage; a LIN-46:GFP fusion protein is detected in the cytoplasm and non-nucleolar part of the nucleus of ventral and lateral hypodermal cells around the time of the larval molts; in addition, the LIN-46 fusion protein is detected in cell bodies and axons of the AVBL/R motor interneurons.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable molecular adaptor activity and molybdopterin molybdotransferase activity. Involved in regulation of development, heterochronic. Located in cytoplasm and nucleus. Expressed in hypodermis; seam cell; and vulval precursor cell.
• Biotype: SO:0001217
• Genetic Position: V :4.77373 ±0.002208
• Length (nt): 1876

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00003031

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:R186.4.1	R186.4.1	1365	V: 12968855-12970730

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:R186.4	R186.4	1176	V: 12968891-12968914

2 RNAi Result

• WBRNAi00052013
• WBRNAi00027735

33 Allele

• gk963271
• gk963301
• gk964458
• gk964459
• WBVar02061627
• tm10752
• WBVar01868754
• WBVar01868753
• bp312
• bp284
• ma164
• ma174
• gk504415
• WBVar01462319
• WBVar01462318
• ma385
• ma467
• gk488869
• gk590124
• gk314243
• gk832361
• gk750861
• gk882116
• WBVar00011495
• gk468998
• gk739742
• gk674752
• gk250689
• gk250687
• gk250688

1 Chromosome

• WormBase ID: V
• Organism: Caenorhabditis elegans
• Length (nt): 20924180

1 Chromosome Location

• Feature . Primary Identifier: WBGene00003031
• Start: 12968855
• End: 12970730
• 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_chrV_12970731..12971109
• Length (nt): 379
• Chromosome Location: V: 12970731-12971109
• Organism: Caenorhabditis elegans

131 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
adult vs dauer larva	Transcripts that showed differential expression in adult vs dauer lava in N2 animals at 20C.	N.A.	WBPaper00050488:adult_vs_dauer_regulated_N2_20C
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when no food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_NoFood
	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
	Genes that showed increased expression in wdr-5(ok1417) comparing with in N2.	Statistical analysis for misexpression was performed using a moderated t test from the package limma. All genes with a false discovery rate (FDR) of <= 5% (p <= 0.05) were selected as differentially regulated.	WBPaper00045861:wdr-5(ok1417)_upregulated
	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
	Transcripts that showed significantly increased expression in ogt-1(ok1474) neuronal cells isolated by FACs comparing to in FACs isolated neuronal cells from wild type.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00066485:ogt-1(ok1474)_upregulated_neuron
	Transcripts that showed significantly higher expression in somatic gonad precursor cells (SGP) vs. head mesodermal cells (hmc).	DESeq2, fold change >= 2, FDR <= 0.01.	WBPaper00056826:SGP_biased
	Genes that showed significantly increased expression in wrn-1(gk99) comparing to in N2, according to RNAseq.	DESeq was used to calculate the fold changes, log fold changes, and significance of the changes for each comparison.	WBPaper00045934:wrn-1(gk99)_upregulated
	Transcripts that showed significantly decreased expression in atfs-1(cmh15) (null allele) animals comparing to in N2 animals at L4 larva stage.	edgeR, fold change > 2, FDR < 0.05	WBPaper00060909:atfs-1(cmh15)_downregulated
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva daf-16(mu86);glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_daf-16(mu86);glp-1(e2141)
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_glp-1(e2141)
	Transcripts that showed significantly increased expression in aak-1(tm1944);aak-2(ok524) animals comparing to in N2.	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:aak-1(tm1944);aak-2(ok524)_upregulated
	Transcripts that showed significantly increased expression in nhr-114(gk849) comparing to wild type animals at L4 larva.	DESeq2 1.26.0, fold change > 2, FDR < 0.05.	WBPaper00064539:nhr-114(gk849)_upregulated
	Transcripts that showed significantly increased expression in alg-1(gk214), comparing to in N2.	DESeq2, Fold change > 1.5.	WBPaper00051404:alg-1(gk214)_upregulated
	Transcripts that showed significantly increased expression in animal with pgph-2 overepxreesion [pgph-2p-pgph-2; myo-2p-mcherry] in glucose excess condition.	Genes with anadjusted P-value <= 0.05 found by DESeq2 were assigned as differentially expressed.	WBPaper00065926:pgph-2(overepxreesion)_upregulated_glucose
	Transcripts that showed significantly increased expression in cco-1(RNAi) comparing to in vector control animals.	The limma package47 was used for differential expression. Genes with a Benjamini-Hochberg adjusted P-value <0.05 and an absolute log fold change of 2 were considered differentially expressed.	WBPaper00053402:cco-1(RNAi)_upregulated
	Transcripts that showed significantly increased expression in wdr-5(ok1417);skn-1(lax188) comparing to in skn-1(lax188) at day 2 adult stage.	fold change > 2	WBPaper00058711:wdr-5(ok1417)_upregulated
	Transcripts that showed significantly increased expression in sftb-1(cer6) deletion homozygous comparing to to in N2 animals at L4 larva stage.	DESeq2, fold change > 2	WBPaper00058725:sftb-1(cer6)_downregulated
	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 oscillating mRNA expression level throughout the 16 hour time courses from L3 larva to young adult.	The following three lines of R code were used to perform the classification: increasing <-2*amplitude-PC1 < -1.7; oscillating <-!increasing & (amplitude > 0.55); flat <-!increasing & !oscillating; Note that the amplitude of a sinusoidal wave corresponds to only half the fold change between trough and peak.	WBPaper00044736:oscillating_dev_expression
	Transcripts that showed significantly increased expression in clk-1(qm30) comparing to in N2.	Differential gene expression analysis was performed using the quasi-likeli-hood framework in edgeR package v. 3.20.1 in R v. 3.4.1.	WBPaper00053810:clk-1(qm30)_upregulated
	Transcripts that showed significantly increased expression in isp-1(qm150) comparing to in N2.	Differential gene expression analysis was performed using the quasi-likeli-hood framework in edgeR package v. 3.20.1 in R v. 3.4.1.	WBPaper00053810:isp-1(qm150)_upregulated
	Transcripts that showed significantly increased expression in nuo-6(qm200) comparing to in N2.	Differential gene expression analysis was performed using the quasi-likeli-hood framework in edgeR package v. 3.20.1 in R v. 3.4.1.	WBPaper00053810:nuo-6(qm200)_upregulated
	Transcripts that showed significantly increased expression among animals treated with 400mM sucrose and 500 mg per ml stearic acid from L1 to L4 larva stage comparing to animals grown up on control plates.	CuffDiff, FDR <= 0.05, fold change >= 2.	WBPaper00059253:sucrose_stearic-acid_upregulated
	Transcripts that showed significantly increased expression in hpk-1(pk1393) comparing to in N2 at adult day 2.	DESeq 2, fold change > 2, FDR < 0.05.	WBPaper00065581:hpk-1(pk1393)_upregulated
	Transcripts that showed significantly increased expression in hda-1(ne4752[3xFLAG-Degron-HDA-1]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:hda-1(ne4752)_upregulated
	Transcripts that showed significantly decreased expression in hpl-2(tm1489) comparing to in N2 animals.	DESeq2, adjusted p-value < 0.05, log2 fold change > 2 or < -2.	WBPaper00054493:hpl-2(tm1489)_downregulated
	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:hypodermis_L3-L4-larva_expressed
	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:PVD-OLL-neurons_L3-L4-larva_expressed
	Transcripts that showed significantly increased expression in hmg-4(RNAi) comparing to in vector control worm at L4 larva stage.	DESeq 2, fold change > 4, adjusted p-value < 0.05.	WBPaper00055013:hmg-4(RNAi)_upregulated

6 Expression Patterns

• Primary Identifier: Expr12872
• Pattern: Green fluorescent protein (GFP) reporter constructs indicated that lin-46 is expressed in hypodermal cells, particularly the lateral and ventral hypodermis, in brief periods during larval development. Animals bearing a transcriptional fusion showed intense fluorescence in lateral hypodermal cells around the time of each molt, especially during the L2- and L4-lethargus. In L2 animals, not all seam cells fluoresced simultaneously, and often only a cluster of an even number of cells fluoresced in a given animal, suggesting the expression of the fusion is related to seam cell division, which occurs somewhat asynchronously during larval development (Sulston and Horvitz, 1977). A lin-46 translational fusion reporter showed a similar expression pattern, although it was less intense. The translational fusion also showed strong constitutive expression in the cell bodies and axons of the bilateral motor interneurons AVB, but we do not know the significance of this expression. The LIN-46:GFP fusion protein localized to both cytoplasm and nucleus, but mostly in the non-nucleolar part of the nucleus. Green fluorescent protein (GFP) reporter constructs indicated that lin-46 is expressed in hypodermal cells, particularly the lateral and ventral hypodermis, in brief periods during larval development. Animals bearing a transcriptional fusion showed intense fluorescence in lateral hypodermal cells around the time of each molt, especially during the L2- and L4-lethargus. In L2 animals, not all seam cells fluoresced simultaneously, and often only a cluster of an even number of cells fluoresced in a given animal, suggesting the expression of the fusion is related to seam cell division, which occurs somewhat asynchronously during larval development (Sulston and Horvitz, 1977).
• Subcellular Localization: The translational fusion also showed strong constitutive expression in the cell bodies and axons of the bilateral motor interneurons AVB, but we do not know the significance of this expression. The LIN-46:GFP fusion protein localized to both cytoplasm and nucleus, but mostly in the non-nucleolar part of the nucleus.

• Primary Identifier: Expr15684
• Pattern: The expression pattern of endogenously tagged LIN- 46::mCherry differs from the pattern previously reported for a lin-46 transcriptional reporter transgene (Pepper et al., 2004): We observed LIN-46::mCherry predominately in hypodermal seam cells and in the ventral hypodermal vulval precursor cells (VPCs) at the L3 and L4 stages. Our finding that LIN-46::mCherry expression is restricted to the L3 and L4 stages, combined with a previous report indicating that lin-46 transcription occurs at all larval stages (Pepper et al., 2004), suggests that lin-46 is post-transcriptionally regulated.

• Primary Identifier: Expr1155653
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2013188
• 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: Expr1010496
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2031420
• 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).

27 GO Annotation

4 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00003031
• Start: 12968855
• End: 12970730
• Strand: 1

27 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 1876

1 Sequence Ontology Term

• Name: gene

8 Strains

• WBStrain00026482
• WBStrain00026483
• WBStrain00040214
• WBStrain00040225
• WBStrain00040230
• WBStrain00047700
• WBStrain00047698
• WBStrain00055650

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrV_12967983..12968854
• Length (nt): 872
• Chromosome Location: V: 12967983-12968854
• Organism: Caenorhabditis elegans