WormMine: Gene WBGene00000149

• WormBase Gene ID: WBGene00000149
• Gene Name: apl-1
• Sequence Name: C42D8.8
• Brief Description: apl-1 encodes two almost identical isoforms orthologous to human Amyloid precursor protein (APP); although native APL-1 is predicted to be membrane-bound until proteolytically cleaved, neuronal expression of a partial N-terminal extracellular region of APL-1 alone, containing either the E1 or the E2 domain, is sufficient for APL-1's normal functions in vivo (molting and morphogenesis, pharyngeal pumping, and progession past the L1 larval stage), indicating that APL-1 functions non-cell-autonomously; apl-1 is widely expressed in neurons, muscle, hypodermis, and supporting cells of larvae and adults; APL-1 contains a Cu(II)-binding domain; overexpressed APL-1 causes abnormal locomotion, infertility, and partial lethality, but the lethality of excess APL-1 can be partially suppressed by hypomorphic sel-12 mutations; apl-1 mutants show vacuoles in hypodermal cells, while having superfically normal neurons; apl-1 genetically interacts with feh-1 to affect pharyngeal pumping, and APL-1 binds the PTB2 domain of FEH-1 in vitro; apl-1 mutations are not suppressed by ced-3 or crt-1 mutations, and thus are unlikely to activate apoptosis or necrosis.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable heparin binding activity and transition metal ion binding activity. Involved in body morphogenesis; ecdysis, collagen and cuticulin-based cuticle; and nematode larval development. Located in cytoplasmic vesicle; neuron projection; and neuronal cell body. Expressed in several structures, including epithelial cell; excretory cell; hermaphrodite gonad; neurons; and somatic nervous system. Used to study Alzheimer's disease. Human ortholog(s) of this gene implicated in several diseases, including APP-related cerebral amyloid angiopathy; Alzheimer's disease 1; traumatic brain injury; and visual epilepsy. Is an ortholog of human APLP2 (amyloid beta precursor like protein 2).
• Biotype: SO:0001217
• Genetic Position: X :-6.17972 ±0.002702
• Length (nt): 4445

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00000149

Genomics

2 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:C42D8.8a.1	C42D8.8a.1	2741	X: 5112422-5116866
Transcript:C42D8.8b.1	C42D8.8b.1	2055	X: 5113100-5116864

Other

2 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:C42D8.8a	C42D8.8a	2061	X: 5113100-5113420
CDS:C42D8.8b	C42D8.8b	2055	X: 5113100-5113420

29 RNAi Result

• WBRNAi00114297
• WBRNAi00114062
• WBRNAi00114141
• WBRNAi00114220
• WBRNAi00078050
• WBRNAi00078051
• WBRNAi00042368
• WBRNAi00024803
• WBRNAi00008517
• WBRNAi00078053
• WBRNAi00027806
• WBRNAi00076211
• WBRNAi00078056
• WBRNAi00078054
• WBRNAi00078058
• WBRNAi00078057
• WBRNAi00063450
• WBRNAi00114021
• WBRNAi00114100
• WBRNAi00114179
• WBRNAi00114256
• WBRNAi00106458
• WBRNAi00078049
• WBRNAi00063451
• WBRNAi00106459
• WBRNAi00106460
• WBRNAi00106461
• WBRNAi00106462
• WBRNAi00078052

99 Allele

• gk964260
• WBVar02063706
• WBVar02063707
• WBVar01758256
• WBVar01758255
• WBVar01758257
• gk960331
• WBVar01878820
• tm385
• gk279745
• ok1697
• WBVar01601725
• WBVar01601726
• WBVar00078578
• WBVar00078575
• WBVar00078577
• WBVar00078576
• WBVar01544470
• WBVar02027054
• WBVar01549631
• WBVar01549632
• WBVar01549633
• gk745570
• WBVar02116364
• gk489857
• gk388863
• gk683700
• gk500821
• gk551358
• gk690576

1 Chromosome

• WormBase ID: X
• Organism: Caenorhabditis elegans
• Length (nt): 17718942

1 Chromosome Location

• Feature . Primary Identifier: WBGene00000149
• Start: 5112422
• End: 5116866
• 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

238 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 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 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
	Transcripts enriched in ASG according to single cell RNAseq.	Genes that pass the Bonferroni threshold for multiple comparisons (q < 0.05) are significantly enriched.	WBPaper00061651:ASG_enriched
	TGF- Dauer pathway adult transcriptional targets. Results obtained by comparing the microarray results of the dauer-constitutive mutants daf-7(e1372), daf-7(m62), and daf-1(m40) with dauer-defective mutants daf-3(mgDf90), daf-5(e1386), and daf-7(e1372);daf-3(mgDf90) double mutants at the permissive temperature, 20C, on the first day of adulthood.	SAM	WBPaper00031040:TGF-beta_adult_upregulated
	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 food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_Food
	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
	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 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 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 that showed significantly increased expression in day 1 adult hermaphrodite comparing to in L4 larva daf-16(mu86);glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-1-adult_vs_L4_upregulated_daf-16(mu86);glp-1(e2141)
	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 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 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
	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 increased expression in daf-2(e1370) comparing to in control animals.	NOIseq(v2.34.0), fold change > = 1.5, Differentially expressed genes (DEGs) were defined as having a probability of differentialexpression > 95%.	WBPaper00064727:daf-2(e1370)_upregulated
	Significantly upregulated genes from clk-1(qm30) microarrays using SAM algorithm with an FDR < 0.1 from adult-only chips.	SAM algorithm with an FDR < 0.1.	WBPaper00033065:clk-1(qm30)_upregulated
	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

15 Expression Patterns

• Primary Identifier: Expr4548
• Pattern: apl-1 expression was detected in more than 50 neuronal, muscle, hypodermal, and supporting cells in adults. The larval expression pattern was similar to the adult pattern with a few exceptions; for instance, apl-1 is expressed in more ventral cord motor neurons in the first larval stage (L1) animals than in other larval stages or adults.

• Primary Identifier: Expr2009360
• 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: Expr1030081
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr15774
• Pattern: We reassessed the expression pattern of APL-1 using a fosmid from the TransgeneOme project in which a genomic copy of APL-1 was tagged with GFP. Overall the expression pattern was similar to those previously described with APL-1 expression detectable in head muscle cells, head neurons as well as the nerve chords. However, an important difference was that APL-1::GFP expression was also detected in the intestine.

• Primary Identifier: Expr2077
• Pattern: Faint expression is seen in larvae and adults, in neuronal cell bodies around the pharynx and processes that comprise the nerve ring. Expression is also occasionally seen in the processes and cell bodies of the ventral nerve cord.

• Primary Identifier: Expr7949
• Remark: Picture: Figure 3, S3, S4.
• Pattern: GFP signals were observed in the head and pharynx, spermatheca, uterus and vulva, some cells in tail and ventral neurons. Strong GFP expression was observed in seam cells. Furthermore, apl-1 expression in seam cells was temporally regulated. The GFP signal in seam cells was not detected (or in rare cases, weakly detected) from L1 to early L4 stages, frequently detected from the mid L4 stage, and almost always detected with high-level expression at late L4 and adult stages. This temporal expression profile of apl-1 was observed in two independent integrated lines of apl-1::gfp::unc-54. No temporal change of apl-1 expression was apparent in any other cells).

• Primary Identifier: Expr9130
• Remark: Picture: Figure 1.
• Pattern: APL-1::GFP fluorescence is detected in the cell bodies and processes of nerve ring interneurons and the ventral cord. apl-1::gfp is also expressed in ocket cells and amphids present in the head. Strong expression is seen in junctional cells such as the pharyngeal intestinal valve, which tethers the pharynx to the intestine, and the uterine seam junction in adults, which provides the structural connection between the epidermis and the uterus. APL-1 can be weakly detected in many epidermal epithelia including hyp7, the hypodermal syncitium surrounding the worm, as well as vulval cells, rectal valve cells, pharyngeal arcade cells, and tail hypodermis. Expression is prominent in the excretory cell, a long H-shaped cell implicated in fluid balance. APL-1 was notably absent from body wall muscle and intestine.
• Subcellular Localization: APL-1::GFP fluorescence is detected in the cell bodies and processes of nerve ring interneurons and the ventral cord.

• Primary Identifier: Expr11408
• Remark: Feature : apl-1 enhancer region.
• Pattern: This 201-bp region is sufficient to drive gfp expression in the seam cells. The expression was low at the early L4 stage, but significantly elevated at the late L4 stage.

• Primary Identifier: Expr11535
• Subcellular Localization: In wild- type worms, APL-1::GFP was expressed in a subset of head, ventral, and sublateral neurons. In particular, along the nerve processes of sublateral neurons, APL-1::GFP localized in a punctate pattern, suggesting that APL-1::GFP is located in the vesicular compartments of the cell.

• Primary Identifier: Chronogram223
• Remark: Original chronogram file: chronogram.1250.xml
• Reporter Gene: [C42D8.8:gfp] transcriptional fusion.

• Primary Identifier: Expr1240
• Pattern: Strong expression at embryo. Strong expression at L1-L4 larva. Weak expression at dauer. Intermediate expression at adult hermaphrodite. Weak expression at adult male.

• Primary Identifier: Expr2027596
• 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: Expr1010947
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr1146353
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Chronogram1556
• Remark: Original chronogram file: chronogram.427.xml
• Reporter Gene: [C42D8.8:gfp] transcriptional fusion.

19 GO Annotation

12 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00000149
• Start: 5112422
• End: 5116866
• Strand: -1

19 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 4445

1 Sequence Ontology Term