WormMine: Gene WBGene00001008

• WormBase Gene ID: WBGene00001008
• Gene Name: dlk-1
• Sequence Name: F33E2.2
• Brief Description: dlk-1 encodes a mitogen-activated protein kinase kinase kinase (MAPKKK) that is the C. elegans ortholog of the dual-leucine zipper MAPKKK; in C. elegans, dlk-1 functions with mkk-4 and pmk-3 in a MAPK signaling pathway that regulates presynaptic development; dlk-1 is also essential for neuron regeneration; DLK-1 abundance is negatively regulated by the RPM-1 E3 ubiquitin ligase which can stimulate DLK-1 ubiquitination; DLK-1 localizes to the periactive zone of synapses in the nerve ring and nerve cord.
• Organism: Caenorhabditis elegans
• Automated Description: Enables ubiquitin protein ligase binding activity. Involved in several processes, including p38MAPK cascade; regulation of axon extension; and sprouting of injured axon. Located in neuronal cell body and synapse. Expressed in PLML and PLMR. Is an ortholog of human MAP3K12 (mitogen-activated protein kinase kinase kinase 12).
• Biotype: SO:0001217
• Genetic Position: I :13.6067 ±0.020734
• Length (nt): 7002

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00001008

Genomics

5 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:F33E2.2b.1	F33E2.2b.1	3100	I: 12565800-12572801
Transcript:F33E2.2a.1	F33E2.2a.1	3121	I: 12565800-12572801
Transcript:F33E2.2e.1	F33E2.2e.1	624	I: 12566129-12567254
Transcript:F33E2.2d.1	F33E2.2d.1	2568	I: 12566129-12570864
Transcript:F33E2.2c.1	F33E2.2c.1	1734	I: 12568973-12572796

Other

5 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:F33E2.2e	F33E2.2e	624	I: 12566129-12566218
CDS:F33E2.2d	F33E2.2d	2568	I: 12566129-12566218
CDS:F33E2.2a	F33E2.2a	2787	I: 12566129-12566218
CDS:F33E2.2b	F33E2.2b	2766	I: 12566129-12566218
CDS:F33E2.2c	F33E2.2c	1734	I: 12568973-12569389

10 RNAi Result

• WBRNAi00113201
• WBRNAi00046215
• WBRNAi00003207
• WBRNAi00003576
• WBRNAi00091030
• WBRNAi00113159
• WBRNAi00113106
• WBRNAi00031721
• WBRNAi00112971
• WBRNAi00075937

159 Allele

• gk962706
• gk963849
• gk964175
• gk963095
• h7747
• WBVar00243738
• gk396346
• gk794008
• gk745712
• gk745711
• gk689921
• gk555459
• gk486196
• gk881273
• gk869533
• gk504124
• gk395409
• gk590839
• gk927421
• gk866578
• gk484187
• gk378981
• gk376806
• gk891531
• gk865852
• gk926884
• gk532622
• gk613604
• gk683412
• gk713569

1 Chromosome

• WormBase ID: I
• Organism: Caenorhabditis elegans
• Length (nt): 15072434

1 Chromosome Location

• Feature . Primary Identifier: WBGene00001008
• Start: 12565800
• End: 12572801
• Strand: -1

4 Data Sets

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

0 Downstream Intergenic Region

186 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly increased expression in L1 neural cells comparing to in adult neural cells.	DESeq2 (v1.18.1) fold change > 2, P-adj<0.05, using BenjaminiHochberg correction.	WBPaper00060811:L1_vs_adult_upregulated_neural
	Transcripts expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
	Genes that showed expression levels higher than the corresponding reference sample (embryonic 24hr 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:all-neurons_L1-larva_expressed
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
	mRNAs that showed decreased expression in 1 cell mebryo comparing to in oocyte, according to RNAseq analysis.	Gaussian error propagation. As cutoff for the up-regulated genes authors used log2 fold change > 1 and P < 0.05 and as cutoff for the down-regulated genes authors used log2 fold change < -1 and P < 0.05.	WBPaper00045420:fertilization_downregulated_transcript
	Genes that showed expression levels higher than the corresponding reference sample (embryonic 24hr 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:AVE-neuron_L1-larva_expressed
	Neuronally enriched transcripts according to a comparison of neuronal nuclei IP samples to total nuclei using isolation of nuclei from tagged specific cell types (INTACT) technology.	DESEQ2, fold change > 2 and FDR < 0.01.	WBPaper00062103:neuron_enriched
	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
Bacteria: E.faecalis strain OG1RF	Transcripts that showed significantly increased expression after infection by E. faecalis OG1RF.	Ballgown was used to calculate differential expression of genes using FPKM data and to generate tables with fold change and P values. Genes were shortlisted with a cutoff of 2-fold change and P values of less than 0.05.	WBPaper00059754:E.faecalis_OG1RF_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
	Genome-wide analysis of developmental and sex-regulated gene expression profile.	self-organizing map	cgc4489_group_18
	Transcripts expressed in the epithelial tissues surrounding the pharynx that includes the arcade and intestinal valve (AIV) cells, according to PAT-Seq analysis using Pbath-15-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:arcade_intestinal-valve_expressed
	Transcripts expressed in body muscle, according to PAT-Seq analysis using Pmyo-3-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:body-muscle_expressed
	Transcripts expressed in GABAergic neuron, according to PAT-Seq analysis using Punc-47-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:GABAergic-neuron_expressed
	Transcripts expressed in hypodermis, according to PAT-Seq analysis using Pdpy-7-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:hypodermis_expressed
	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 expressed in intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Transcripts expressed in NMDA neuron, according to PAT-Seq analysis using Pnmr-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:NMDA-neuron_expressed
	Transcripts expressed in pharynx, according to PAT-Seq analysis using Pmyo-2-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:pharynx_expressed
	Transcripts expressed in seam cells, according to PAT-Seq analysis using Pgrd-10-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:seam_expressed
	Genes with expression level regulated by genotype (N2 vs CB4856) 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_regulated_aging
	Genes with expression level regulated by genotype (N2 vs CB4856) at Late reproduction stage (96 hours at 24 centigrade).	Authors permuted transcript values and used a genome-wide threshold of log10 P-value = 2, which resembles a false discovery rate (FDR) of 0.0118.	WBPaper00040858:eQTL_regulated_reproductive
	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 expressed in vulva.	FPKM >= 1.	WBPaper00064122:vulva_transcriptome
	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
	Transcripts that showed significantly increased expression in mrg-1(qa6200) comparing to in control animals in primordial germ cells (PGCs) at L1 larva stage.	DESeq2(v1.32.0), FDR < 0.05.	WBPaper00064315:mrg-1(qa6200)_upregulated_PGCs
	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 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 detected in body muscle nuclei according to a nuclear FACS-based strategy.	Cufflinks	WBPaper00065120:body-muscle-transcriptome

10 Expression Patterns

• Primary Identifier: Expr1030629
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr8637
• Remark: Picture: Fig 5.
• Pattern: DLK-1::GFP showed restricted expression in neurons and pharynx.
• Subcellular Localization: In neurons, DLK-1::GFP was localized to presynaptic regions. DLK-1::GFP localized adjacent to but not overlapping with SNT-1 or Rim/UNC-10.

• Primary Identifier: Expr8644
• Remark: Picture: Fig. 5G, 5H.
• Subcellular Localization: GFP::DLK-1 protein was present both in neuron cell bodies (near the membrane and excluded from the nucleus and in ventral cord neurites in a punctate pattern.

• Primary Identifier: Expr1150102
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2010950
• 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: Expr12042
• Pattern: A reporter composed of 3 kb dlk-1 promoter confirmed that dlk-1 was expressed at low level in the PLM.

• Primary Identifier: Expr2029189
• 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: Expr1015860
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr12623
• Subcellular Localization: DLK-1::GFP expressed from the ASI specific gpa-4 promoter mostly localized to the dendrites and axons of these neurons. The protein accumulated at the base of the cilium, but was only occasionally detected at very low levels inside the cilium. DLK-1::GFP was present as a diffuse signal and as punctae in the dendrites as well as in the cytoplasm, in accordance with previous observations.

• Primary Identifier: Expr16462
• Subcellular Localization: DLK-1::GFP displayed diffuse and punctate patterns. We analyzed colocalization of DLK-1::GFP with XBX- 1::tagRFP(cas502), representing the dynein light intermediate chain of IFT. By confocal imaging analysis, we detected some DLK-1::GFP puncta to be close to, or partly overlapping with, XBX-1::tagRFP puncta in cilia.

44 GO Annotation

3 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00001008
• Start: 12565800
• End: 12572801
• Strand: -1

44 Ontology Annotations

2 Regulates Expr Cluster

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly decreased expression in dlk-1(km12) animals, comparing to in N2 animals at L4 larva stage.	DESeq2 FDR < 0.05	WBPaper00059604:dlk-1(km12)_downregulated
	Transcripts that showed significantly increased expression in dlk-1(km12) animals, comparing to in N2 animals at L4 larva stage.	DESeq2 FDR < 0.05	WBPaper00059604:dlk-1(km12)_upregulated

1 Sequence

• Length: 7002

1 Sequence Ontology Term