WormMine: Gene WBGene00000913

• WormBase Gene ID: WBGene00000913
• Gene Name: daf-18
• Sequence Name: T07A9.6
• Brief Description: daf-18 encodes a lipid phosphatase homologous to the human PTEN tumor suppresor (OMIM:601728, mutated in Cowden disease and several cancers); DAF-18 negatively regulates insulin-like signaling mediated by DAF-2/IR and AGE-1/PI3K and thus plays a role in metabolism, development, and longevity; based on sequence and genetic analysis, DAF-18 is predicted to dephosphorylate AGE-1-generated PIP3 in order to limit activation of the downstream AKT-1 and AKT-2 kinases that negatively regulate DAF-16.
• Organism: Caenorhabditis elegans
• Automated Description: Enables protein tyrosine phosphatase activity. Involved in several processes, including determination of adult lifespan; positive regulation of dauer larval development; and positive regulation of positive chemotaxis. Acts upstream of with a positive effect on protein import into nucleus. Located in several cellular components, including axon; cytoplasmic side of plasma membrane; and somatodendritic compartment. Expressed in several structures, including Z2; egg-laying apparatus; germ line; oocyte; and somatic nervous system. Used to study cancer. Human ortholog(s) of this gene implicated in several diseases, including carcinoma (multiple); coronary artery disease (multiple); and gastrointestinal system cancer (multiple). Is an ortholog of human PTEN (phosphatase and tensin homolog).
• Biotype: SO:0001217
• Genetic Position: IV :-26.0114 ±0.005797
• Length (nt): 5167

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00000913

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:T07A9.6.1	T07A9.6.1	3333	IV: 420011-425177

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:T07A9.6	T07A9.6	2889	IV: 420426-420545

59 RNAi Result

• WBRNAi00084942
• WBRNAi00084936
• WBRNAi00079100
• WBRNAi00114372
• WBRNAi00067933
• WBRNAi00052706
• WBRNAi00108035
• WBRNAi00108037
• WBRNAi00108065
• WBRNAi00108066
• WBRNAi00108076
• WBRNAi00108079
• WBRNAi00108080
• WBRNAi00108084
• WBRNAi00092161
• WBRNAi00092162
• WBRNAi00108078
• WBRNAi00092160
• WBRNAi00018333
• WBRNAi00108056
• WBRNAi00109610
• WBRNAi00030224
• WBRNAi00109222
• WBRNAi00079093
• WBRNAi00008024
• WBRNAi00079099
• WBRNAi00079086
• WBRNAi00079085
• WBRNAi00079088
• WBRNAi00079090

95 Allele

• gk963722
• gk963025
• gk963557
• gk963558
• gk963690
• gk963402
• gk963403
• gk963324
• gk963325
• gk192013
• gk192014
• gk192015
• gk192016
• gk192017
• gk192018
• gk192019
• WBVar01607516
• WBVar01607515
• WBVar01607518
• WBVar01607517
• WBVar01607519
• WBVar01607521
• WBVar01607520
• WBVar01607523
• WBVar01607522
• WBVar00182829
• gk945301
• WBVar01823381
• tm5119
• tm5288

1 Chromosome

• WormBase ID: IV
• Organism: Caenorhabditis elegans
• Length (nt): 17493829

1 Chromosome Location

• Feature . Primary Identifier: WBGene00000913
• Start: 420011
• End: 425177
• 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_chrIV_419959..420010
• Length (nt): 52
• Chromosome Location: IV: 419959-420010
• Organism: Caenorhabditis elegans

220 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Genes with expression altered >= 3-fold in dpy-10(e128) mutants.	Data across the wild type series was analyzed using the Significance analysis of Microarrays (SAM) algorithm (to calculate the False Discovery Rate (FDR)).	WBPaper00035873:dpy-10_regulated
	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
	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
	Proteins interacting with NHR-49-GFP according to co-IP and LC-MS.	N.A.	WBPaper00064071:NHR-49_interacting
	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 intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Transcripts expressed in pharynx, according to PAT-Seq analysis using Pmyo-2-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:pharynx_expressed
	Genes with expression level regulated by genotype (N2 vs CB4856) and age at L3 larva and Late reproduction stage (96 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_developing
	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 3 adult hermaphrodite comparing to in L4 larva fem-3(q20) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_upregulated_fem-3(q20)
Bacteria diet: Sphingomonas aquatilis Yellow. Fed for 30 generations.	Transcripts that showed significantly decreased expression after fed by bacteria Sphingomonas aquatilis (Yellow) for 30 generations comparing to animals fed by E. coli OP50.	DESeq2 fold change > 2, p-value < 0.01.	WBPaper00061007:S.aquatilis_downregulated
	Transcripts detected in germline isolated from day-1 adult hermaphrodite animals.	All three experiments have CPM >= 1.	WBPaper00067147:germline_expressed
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 10 mix) vs BT407 6h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.1mix_downregulated_6h
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 10 mix) vs BT407 12h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.1mix_downregulated_12h
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 2 mix) vs BT407 6h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.5mix_downregulated_6h
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 2 mix) vs BT407 12h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.5mix_downregulated_12h
	Transcripts that showed significantly decreased expression in hsp-6(mg585) comparing to in N2 at L4 larva stage.	EdgeR, fold change > 2, FDR < 0.001.	WBPaper00056290:hsp-6(mg585)_downregulated
	Transcripts that showed significantly decreased expression in skn-1gf(lax188) comparing to in N2 animals at L4 stage fed with OP50 and exposed to PA14 for 4 hours.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00067255:skn-1(lax188)_downregulated_PA
	Transcripts that showed significantly increased expression in enriched nuclei of daf-2(e1370) comparing to in wild type nuclei.	edgeR, fold change > 2, FDR < 0.05	WBPaper00067267:daf-2(e1370)_upregulated_nuclei
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 increased expression in animals exposed to 400uM tamoxifen from L1 to L4 larva stage.	DEseq2, fold change > 2	WBPaper00064505:tamoxifen_upregulated
	Transcripts that showed significantly increased expression after 24-hour exposure to 10uM benzyl butyl phthalate (BBP) in col-121(nx3) animals.	DESeq2v1.38.3, FDR < 0.05	WBPaper00067417:benzyl-butyl-phthalate_regulated
	Significantly differentially expressed genes as determined by microarray analysis of wild-type and cde-1 mutant germlines.	RNAs that changed at least 2-fold with a probability of p < 0.05 were considered differentially regulated between wildtype and cde-1.	WBPaper00035269:cde-1_regulated
Transgeneration hypoxia treatment.	Transcripts that are significantly upregulated in F1 animals after P0 parents were exposed to 0.1% oxygen for 16 hours at L4 larva stage.	For calling the significant differentially expressed genes (DEGs),the false discovery rate (FDR) after multiple testing correction was set as 0.05 and analyzed in edgeR.	WBPaper00064871:hypoxia_upregulated_F1
Heat Shock: 35C 4 hours at L4 larva stage.	Transcripts that showed significantly decreased expression after L4 larva N2 animals were heat stressed at 35C for 4 hours	DESeq2	WBPaper00057154:HeatShock_downregulated_mRNA
	Genes down regulated by mir-243(n4759).	RNAs that changed at least 2-fold with a probability of p > 0.05 in three biological replicates were considered differentially regulated between wild-type and mir-243.	WBPaper00036130:mir-243_down_regulated
25C vs. 20C	Transcripts that showed significantly increased expression in 1-day post L4 adult hermaphrodite N2 grown at 25C, comparing to in N2 animals grown at 20C.	CuffDiff, fold change > 2.	WBPaper00065096:25C_vs_20C_upregulated

13 Expression Patterns

• Primary Identifier: Expr4267
• Subcellular Localization: Functional DAF-18::Venus was localized to the surface of the cell body, dendrite, and axon, but not to the cilia.

• Primary Identifier: Expr1030574
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr16002
• Pattern: We observed widespread expression of daf-18 genomic GFP, including within the intestine, neurons, and hypodermis. We did not observe expression from our daf-18(+) genomic transgene in the PGCs.

• Primary Identifier: Expr3767
• Remark: Reporter gene fusion type not specified.
• Pattern: Widespread GFP expression was observed in embryos from the bean stage onwards. During larval development, GFP expression revealed that the daf-18 promoter was active in many if not all tissues, including the intestine, neurons, body wall muscles, seam cells and hypodermis, with elevated GFP levels in a few head neurons and in the intestine from L1 to adult stage at 15 centigrades and 25 centigrades. A wide up-regulation of GFP levels in many if not all tissues was observed during the transition between L1 and pre-dauer L2D stage. Once dauer tissues were fully remodeled, high GFP levels were then limited to head neurons and ventral and dorsal nerve cords.

• Primary Identifier: Expr8834
• Remark: In the overexpressing line (quIs18) DAF-18/PTEN's neuronal expression is restricted to a subset of the head amphid neurons and is expressed weakly in the nerve cord. DAF-18::GFP was also detected in the amphids and ventral nerve cord. Picture: Fig 2.
• Pattern: Immuno-histochemistry experiments reveal that DAF-18/PTEN and VAB-1/EphR are both expressed in the Z2/Z3 germline precursor cells, oocytes, as well as neuronal tissues. In the neuronal tissues, VAB-1/EphR is localized to the ventral nerve cord, nerve ring, and some head neurons.
• Subcellular Localization: VAB-1/EphR is expressed on the membrane of the proximal oocytes, whereas DAF-18/PTEN appears to show membrane and nuclear expression of multiple oocytes in both hermaphrodites and females.

• Primary Identifier: Expr3842
• Pattern: daf-18 message was present predominantly in the germline in larvae and adults (93%, n = 88). This is a specific signal not detected in the daf-18 deletion mutant (n = 89) or in glp-4(bn2) animals (n = 112), where little germline proliferation occurs.

• Primary Identifier: Expr10551
• Pattern: DAF-18::GFP expression was observed in many tissues during all larval stages, including the developing vulva, the uterus, the ventral nerve cord and the distal tip cells. In particular, equal levels of DAF-18::GFP expression were detected in the six VPCs of L2 larvae, and expression persisted in the descendants of the induced VPCs until the Pn.pxxx stage. Besides the vulval cells, the DAF-18::GFP reporter was also expressed at the L3 to L4 larval stages in several cells of the uterus, which is part of the somatic gonad.
• Subcellular Localization: The sub-cellular localization of DAF-18::GFP changed over the course of vulval development. In the VPCs of L2 larvae prior to and during induction (Pn.p stage), DAF-18::GFP was predominantly localized in the cytoplasm and the nucleus. However, at the subsequent stages (Pn.px to Pn.pxx stages), DAF- 18::GFP became increasingly localized to the plasma membrane of the vulval cells. Plasma membrane staining peaked at the 'Christmas tree' (Pn.pxxx) stage, when almost all the protein appeared to be localized to the membranes and nuclear staining was reduced to very low levels.

• Primary Identifier: Expr2010766
• 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: Expr1020047
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr1156316
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2029003
• 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: Expr14624
• Subcellular Localization: Expression of all these three mCherry-fused DAF-18/PTEN proteins was detected, and their subcellular localization was enriched at the plasma membrane.

• Primary Identifier: Expr14625
• Subcellular Localization: KIN-4::GFP and mCherry-tagged DAF-18 (mCherry::DAF-18) co-localized to the cytoplasm of neurons.

81 GO Annotation

6 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00000913
• Start: 420011
• End: 425177
• Strand: -1

81 Ontology Annotations

6 Regulates Expr Cluster

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly decreased expression in strain GC1459 containing daf-18(ok480) comparing to control strain GC1171.	edgeR, p-value < 0.05, fold change > 2.	WBPaper00061699:daf-18(ok480)_downregulated
	Transcripts that showed significantly decreased expression in daf-2(e1370); daf-18(nr2037) comparing to in daf-2(e1370) animals.	Differentially expressed genes (fold change > 2 and adjusted p value < 0.05) were identified by using DESeq2 (v.1.22.2).	WBPaper00061952:daf-18(nr2037)_downregulated
	Transcripts that showed significantly decreased expression in daf-2(e1370); daf-18(yh1) comparing to in daf-2(e1370) animals.	Differentially expressed genes (fold change > 2 and adjusted p value < 0.05) were identified by using DESeq2 (v.1.22.2).	WBPaper00061952:daf-18(yh1)_downregulated
	Transcripts that showed significantly increased expression in strain GC1459 containing daf-18(ok480) comparing to control strain GC1171.	edgeR, p-value < 0.05, fold change > 2.	WBPaper00061699:daf-18(ok480)_upregulated
	Transcripts that showed significantly increased expression in daf-2(e1370); daf-18(nr2037) comparing to in daf-2(e1370) animals.	Differentially expressed genes (fold change > 2 and adjusted p value < 0.05) were identified by using DESeq2 (v.1.22.2).	WBPaper00061952:daf-18(nr2037)_upregulated
	Transcripts that showed significantly increased expression in daf-2(e1370); daf-18(yh1) comparing to in daf-2(e1370) animals.	Differentially expressed genes (fold change > 2 and adjusted p value < 0.05) were identified by using DESeq2 (v.1.22.2).	WBPaper00061952:daf-18(yh1)_upregulated

1 Sequence

• Length: 5167

1 Sequence Ontology Term

• Name: gene

13 Strains

• WBStrain00030724
• WBStrain00030758
• WBStrain00031447
• WBStrain00051731
• WBStrain00051733
• WBStrain00051734
• WBStrain00051685
• WBStrain00054859
• WBStrain00054858
• WBStrain00054857
• WBStrain00004234
• WBStrain00004311
• WBStrain00000135

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrIV_425178..426167
• Length (nt): 990
• Chromosome Location: IV: 425178-426167
• Organism: Caenorhabditis elegans