WormMine: Gene WBGene00001487

• WormBase Gene ID: WBGene00001487
• Gene Name: frk-1
• Sequence Name: T04B2.2
• Brief Description: frk-1 encodes a non-receptor tyrosine kinase orthologous to the human proto-oncogene Fer; frk-1 is an essential gene required early for embryonic cell proliferation and later in embryonic epidermal cells for enclosure, morphogenesis and late stages of differentiation; FRK-1's role in embryonic development is independent of its kinase domain, and when expressed in cultured mammalian cells, FRK-1 disrupts cell adhesion; FRK-1 is initially expressed in all cells of the early embryo where it localizes to nuclei and points of cell-cell contact; later expression is seen in epithelial cells, body wall muscle, and the adult germline, including mature sperm; FRK-1 expression in epidermal cells requires activity of the ELT-1 GATA transcription factor, and FRK-1 localization to the plasma membrane requires PAT-3/Beta-integrin, JAC-1/p120 catenin, and HMP-2/Beta-catenin with which FRK-1 interacts in vitro.
• Organism: Caenorhabditis elegans
• Automated Description: Enables beta-catenin binding activity and protein kinase activity. Involved in several processes, including embryonic body morphogenesis; negative regulation of canonical Wnt signaling pathway; and regulation of epidermal cell differentiation. Located in several cellular components, including cell-cell junction; nucleus; and plasma membrane. Expressed in several structures, including germ line; hermaphrodite gonad; hypodermis; intestine; and sperm. Human ortholog(s) of this gene implicated in esophagus squamous cell carcinoma; hepatocellular carcinoma; and lung adenocarcinoma. Is an ortholog of human FER (FER tyrosine kinase) and FES (FES proto-oncogene, tyrosine kinase).
• Biotype: SO:0001217
• Genetic Position: IV :4.4713 ±0.000971
• Length (nt): 2559

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00001487

Genomics

4 Transcripts

Class	WormMine ID	Sequence Name	Length (nt)	Chromosome Location
MRNA	Transcript:T04B2.2a.1	T04B2.2a.1	1412	IV: 10043181-10045739
NcPrimaryTranscript	Transcript:T04B2.2c	T04B2.2c	1269	IV: 10043183-10045598
MRNA	Transcript:T04B2.2a.2	T04B2.2a.2	1398	IV: 10043812-10045739
NcPrimaryTranscript	Transcript:T04B2.2b	T04B2.2b	1251	IV: 10043818-10045598

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:T04B2.2a	T04B2.2a	1173	IV: 10044263-10044564

23 RNAi Result

• WBRNAi00099030
• WBRNAi00099028
• WBRNAi00052351
• WBRNAi00018119
• WBRNAi00061009
• WBRNAi00061010
• WBRNAi00061011
• WBRNAi00061012
• WBRNAi00061013
• WBRNAi00061014
• WBRNAi00061015
• WBRNAi00099033
• WBRNAi00099034
• WBRNAi00099037
• WBRNAi00099036
• WBRNAi00035124
• WBRNAi00099038
• WBRNAi00110391
• WBRNAi00023569
• WBRNAi00099039
• WBRNAi00099041
• WBRNAi00099042
• WBRNAi00099044

33 Allele

• gk964278
• gk964078
• gk964500
• gk962765
• gk429401
• gk852973
• WBVar02058583
• ok760
• WBVar00191633
• gk210081
• gk210079
• WBVar01856575
• gk210080
• WBVar02037056
• WBVar01828125
• gk645339
• gk434180
• gk924917
• gk341147
• WBVar00602774
• gk335182
• gk795484
• gk394679
• gk849485
• tm10434
• WBVar01795143
• gk906717
• gk907103
• gk810873
• gk454974

1 Chromosome

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

1 Chromosome Location

• Feature . Primary Identifier: WBGene00001487
• Start: 10043181
• End: 10045739
• 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_10045740..10047407
• Length (nt): 1668
• Chromosome Location: IV: 10045740-10047407
• Organism: Caenorhabditis elegans

180 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
	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
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 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 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_upregulated
	Transcripts that showed significantly increased expression after animals were treated with 50uM Rifampicin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin_upregulated
	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)
	Transcripts that showed significantly increased expression after 24 hours of induction of human beta Amyloid at young adult stage	A 2-fold change in expression level and a false discovery rate analog of p < 0.05.	WBPaper00064130:Beta-Amyloid_24h_upregulated_mRNA
Bacteria infection: Bacillus thuringiensis	Transcripts that showed significantly increased expression in N2 animals infected by bacteria BMB171/Cry5Ba, an acrystalliferous Bt mutant BMB171 transformed with toxin gene cry5Ba on the shuttle vector pHT304, comparing to N2 animals infected by BMB171/pHT304.	N.A.	WBPaper00064229:B.thuringiensis-Cry5Ba_upregulated
	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 increased expression in hrde-1(tm1200) animals, comparing to in N2, after growing at 25C for five generations (late generation).	CuffDiff2	WBPaper00051265:F4_hrde-1(tm1200)_upregulated
	mRNAs that showed increased expression in P-granule RNAi animales (simultaneously targeting pgl-1, pgl-3, glh-1 and glh-4) comparing to in control RNAi animals. Set 1 transcripts were defined as P-value < 0.05 and fold change > 2.	DESeq was used. Fold change between the average of the four control replicates and the average of the four test replicates was used to calculate the significance using a negative binomial distribution. An adjusted P-value was calculated using the Benjamini-Hochberg method for multiple testing correction.	WBPaper00046805:P-granule-RNAi_upregulated_Set1
	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
	Transcripts that showed significantly altered expression after 24 hour exposure to stavudine (d4T) starting at L1 lava stage.	DESeq	WBPaper00053302:stavudine_24h_regulated
	Transcripts that showed significantly decreased expression in Day 5 (5-days post-L4) vs. Day 0 (L4 larva) of adulthood N2 animals.	Differential expression for both small RNA- and mRNA-seq data was tested using DESeq2; P-values were adjusted for multiple testing by Benjamini-Hochberg method.	WBPaper00053318:Aging_downregulated_mRNA_N2
	Transcripts that showed significantly decreased expression in mir-71(n4115) comparing to in N2 at 4-days post L4 adult hermaphrodite.	Differential expression for both small RNA- and mRNA-seq data was tested using DESeq2; P-values were adjusted for multiple testing by Benjamini-Hochberg method.	WBPaper00053318:mir-71(n4115)_downregulated_mRNA
	Transcripts that showed significantly decreased expression in dissected female germline comparing to in dissected male germline.	Log2 Fold change > 2 or <-1, p-value < 0.05.	WBPaper00053599:female_vs_male_downregulated
	Transcripts that showed significantly increased expression in 10-days post L4 adult hermaphrodite npr-8(ok1439) animals grown at 25C, comparing to in N2 animals.	CuffDiff, fold change > 2.	WBPaper00065096:npr-8(ok1439)_upregulated_Day10_25C
Temprature shift to 28C for 24 hours.	Transcripts that showed significantly decreased expression after animals were exposed to 28C temperature for 24 hours.	Differentially expressed genes wereidentified using DESeq (v.1.18.0) by normalizing readsbased on the negative binomial distribution method andcomparing each HS timepoint to the 0-h control.	WBPaper00061341:28C_24h_downregulated
	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:all-neurons_L2-larva_expressed
	Proteins that showed significantly decreased expression after 1-day-old wild type adults were exposed to cisplatin (300ug per mL) for 6 hours.	The differential expression analysis was performed in R. Differentially expressed proteins were identified by using a two-sided t-test on log-transformed data.	WBPaper00065373:Cisplatin_downregulated_WT
	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
	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:coelomocytes_L2-larva_expressed
	Transcripts that showed significantly increased expression in mbl-1(syb4318), referred to as mbl-1short(ex7-), comparing to in N2 at L4 larva stage.	DESeq2, Fold change > 2 and FDR < 0.05	WBPaper00066410:mbl-1(syb4318)_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

8 Expression Patterns

• Primary Identifier: Expr1030888
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr3701
• Pattern: Using two independent antibodies elicited to two different FRK-1 peptides, FRK-1 was initially present both in nuclei and at cell-cell contact points of all cells in early embryos. Expression later became restricted to epithelial cells, body wall muscle and the germline, including mature sperm. Staining was eliminated in frk-1(RNAi) embryos, confirming specificity of the antibody. Epidermal expression of FRK-1, which is apparently sufficient for morphogenesis, requires ELT-1, a transcription factor required to generate all epidermal cells: FRK-1 was seen only in body wall muscle cells in late elt-1(zu180) mutant embryos.
• Subcellular Localization: Localization of FRK-1 to nuclei correlates with phases of active cell division: nuclear localization was prominent in early embryos and the adult germline. The protein remained in the nucleus and at the cell surface until shortly before embryonic enclosure, at which stage most cells became mitotically inactive and nuclear FRK-1 became undetectable. In elongated embryos, FRK-1 was present in the cytoplasm and at the membrane of epidermal cells; cell surface staining was especially prominent in the seam cells. While nuclear function for FRK-1 in morphogenesis cannot be excluded, the protein was not detectable in nuclei during this phase of development. Later, during larval development, FRK-1 reappeared in the nuclei of seam cells and in the nuclei of the developing germline, correlated with their active post-embryonic division. In the adult soma, FRK-1 stably localized to apical junctions of the intestine and somatic cells of the gonad.

• Primary Identifier: Expr12446
• Pattern: A fusion between the frk-1 promoter region and nGFP shows the frk-1 promoter to be active primarily in epithelial cell types, including the hypodermis, intestine and germline uterine and spermathecal lining. Specifically, frk-1 expression is observed in the developing seam cells during embryogenesis and larval development.

• Primary Identifier: Expr12447
• Remark: Asymmetric localization.
• Subcellular Localization: Under wildtype conditions, in actively dividing seam cells (L1 to L2), FRK-1 mimics POP-1 asymmetric localization such that both proteins exhibit higher levels in the anterior nucleus and low levels in the corresponding posterior.

• Primary Identifier: Expr2011880
• 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: Expr1025217
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2030118
• 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: Expr1155979
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

37 GO Annotation

12 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00001487
• Start: 10043181
• End: 10045739
• Strand: 1

37 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 2559

1 Sequence Ontology Term

• Name: gene

1 Strains

• WBStrain00035871

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrIV_10042433..10043180
• Length (nt): 748
• Chromosome Location: IV: 10042433-10043180
• Organism: Caenorhabditis elegans