WormMine: Gene WBGene00006600

• WormBase Gene ID: WBGene00006600
• Gene Name: tph-1
• Sequence Name: ZK1290.2
• Brief Description: tph-1 encodes tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting first step in serotonin biosynthesis; in vivo, tph-1 activity is required for serotonin biosynthesis, and well-fed animals mutant for tph-1 exhibit changes in behavioral and metabolic processes similar to those caused by starvation: slower rates of egg laying and pharyngeal pumping, dauer larval arrest, increased fat storage, and an extended reproductive lifespan; genetic studies indicate that, in regulating feeding and metabolism, tph-1 interacts with the daf-7/TGF-beta and daf-2/insulin-like signaling pathways; a TPH-1::GFP reporter is expressed in the serotonergic neurons: NSM, ADF, HSN (hermaphrodite-specific), CP (male-specific), and also rarely in the AIM and RIH neurons.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable tryptophan 5-monooxygenase activity. Involved in several processes, including determination of adult lifespan; locomotory exploration behavior; and positive regulation of transforming growth factor beta receptor signaling pathway. Located in cytosol and neuron projection. Expressed in CP neuron; nerve ring; and pharynx. Used to study alcohol use disorder and cocaine abuse. Human ortholog(s) of this gene implicated in several diseases, including Alzheimer's disease; alcohol use disorder; attention deficit hyperactivity disorder; and autistic disorder. Is an ortholog of human TPH1 (tryptophan hydroxylase 1) and TPH2 (tryptophan hydroxylase 2).
• Biotype: SO:0001217
• Genetic Position: II :0.504594 ±5.8e-05
• Length (nt): 2649

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00006600

Genomics

2 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:ZK1290.2a.1	ZK1290.2a.1	1828	II: 7549335-7551983
Transcript:ZK1290.2b.1	ZK1290.2b.1	1747	II: 7549377-7551904

Other

2 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:ZK1290.2a	ZK1290.2a	1599	II: 7549358-7549443
CDS:ZK1290.2b	ZK1290.2b	1290	II: 7550081-7550309

9 RNAi Result

• WBRNAi00059211
• WBRNAi00021865
• WBRNAi00027046
• WBRNAi00027047
• WBRNAi00027880
• WBRNAi00114357
• WBRNAi00027556
• WBRNAi00102730
• WBRNAi00114348

38 Allele

• gk963801
• gk963053
• gk962682
• tm11192
• gk147109
• gk931457
• n4622
• mg280
• WBVar02108149
• h13187
• gk790042
• gk740016
• gk353170
• gk825712
• gk479812
• gk445363
• gk572613
• gk869588
• gk595534
• gk786579
• gk576548
• gk765708
• WBVar01934971
• mg180
• tm6950
• gk960372
• gk147104
• gk147106
• gk147105
• WBVar01982535

1 Chromosome

• WormBase ID: II
• Organism: Caenorhabditis elegans
• Length (nt): 15279421

1 Chromosome Location

• Feature . Primary Identifier: WBGene00006600
• Start: 7549335
• End: 7551983
• 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

76 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 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
	Single-cell RNA-Seq cell group 84_0 expressed in neuron.	scVI 0.6.0	WBPaper00065841:84_0
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 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
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
	Genome-wide analysis of developmental and sex-regulated gene expression profile.	self-organizing map	cgc4489_group_18
	Genes significantly enriched in NSM neurons (isolated by FACS) versus the reference, according to RNAseq analysis towards total RNA.	Gene expression quantification and differential expression was analyzed using cufflinks v2.2.1. Enriched contains only genes significantly enriched (differentially expressed >= 2.4 fold in total RNA or >= 3.2 fold in DSN treated total RNA) in the NSM neurons versus the reference.	WBPaper00045974:NSM_enriched_totalRNA_RNAseq
	Transcripts that showed significantly increased expression in hda-1(RNAi) embryos comparing to control animals.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00067044:hda-1(RNAi)_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 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 increased expression in hda-2(ok1479) comparing to in N2 animals.	DESeq2 (version 1.28.1), FDR < 0.01, fold change > 2.	WBPaper00062159:hda-2(ok1479)_upregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Psora and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Psora-Allantoin_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Rapamycin and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Allantoin_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Rapamycin and 50mM Metformin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Metformin_downregulated
	Transcripts that showed significantly decreased 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_downregulated
	Transcripts that showed significantly increased expression in ilc-17.1(syb5296) comparing to in N2 animals at L4 larva stage.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00066594:ilc-17.1(syb5296)_upregulated
	Transcripts that showed significantly decreased expression in set-2(tm1630) animals at embryo stage, comparing to in N2 animals.	DESeq2 (v2.1.8.3) was used to determine DE genes and to generate principal component and scatter plots. DE genes with FDR < 0.05 were analysed using g:Profiler with Bonferroni correction.	WBPaper00060014:set-2(tm1630)_downregulated
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(+), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(+)_vs_control_day2-adult
	Genes significantly enriched in NSM neurons (isolated by FACS) versus the reference, according to tiling array analysis towards total RNA.	A linear model and moderated t-statistic were used to determine differentially expressed genes as implemented by the limma package (v3.21.4). Enriched list contains only genes significantly enriched in the NSM neurons versus the reference <=1.5X and <= 5% FDR.	WBPaper00045974:NSM_enriched_totalRNA_tiling
	Transcripts that showed significantly increased expression in daf-2(e1370) neurons comparing to in N2 neurons at day 8adult stage.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00066978:daf-2(e1370)_upregulated_neuron
	Transcripts that showed significantly increased expression in daf-16(mu86);daf-2(e1370) neurons comparing to in daf-2(e1370) neurons at day 8adult stage.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00066978:daf-16(mu86)_upregulated_neuron
Bacteria infection: Pseudomonas aeruginosa PA14. 24 hours of exposure at 25C.	Transcripts that showed significantly decreased expression in N2 animals with 24 hours of exposure to P. aeruginosa PA14 for 24 hrs at 25C, comparing to N2 animals without exposure to PA14.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00058948:PA14_downregulated
	Transcripts that showed differential expression in dauer mir-34(gk437) vs dauer mir-34(OverExpression) animals at 20C.	N.A.	WBPaper00050488:mir-34(gk437)_vs_mir-34(OverExpression)_regulated_dauer_20C
	Transcripts that showed significantly increased expression in fmi-1(rh308) young adults comparing to in N2 animals.	fold change > 2, p-value < 0.05	WBPaper00066618:fmi-1(rh308)_upregulated
control(maintained under normal lab light (mostly dark, in incubators).) vs EtBr-exposed(maintained under normal lab light (mostly dark, in incubators) and exposed to EtBr (5ug/mL in agar).) at just prior to the third UVC dose (48h).	Genes differentially expressed in control vs under EtBr treatment without UVC exposure, at the -1h timepoint.	Transcripts were defined as fold-change >1.2, p < 0.05 based on Rosetta Resolver analysis for all pairwise treatment comparisons. The fold-change refers to the second intensity over the first.	WBPaper00041939:control_vs_EtBr-exposed_48h
control(maintained under normal lab light (mostly dark, in incubators).) vs UVC-EtBr-exposed(exposed to 7.5 J/m2 UVC radiation 3 times, 24 h apart (48 h total) and exposed to EtBr (5ug/mL in agar).) at just prior to the third UVC dose (48h).	Genes differentially expressed in control vs after UVC exposure and EtBr treatment at the -1h timepoint (just prior to the third UVC dose (48h)).	Transcripts were defined as fold-change >1.2, p < 0.05 based on Rosetta Resolver analysis for all pairwise treatment comparisons. The fold-change refers to the second intensity over the first.	WBPaper00041939:control_vs_UVC-EtBr-exposed_48h
control(maintained under normal lab light (mostly dark, in incubators).) vs UVC-EtBr-exposed(exposed to 7.5 J/m2 UVC radiation 3 times, 24 h apart (48 h total) and exposed to EtBr (5ug/mL in agar).) at 3 h after the third UVC dose (51h), which is also 3 h after being placed on food.	Genes differentially expressed in control vs after UVC exposure and EtBr treatment at the 3h timepoint (3 h after the third UVC dose (51h), which is also 3 h after being placed on food).	Transcripts were defined as fold-change >1.2, p < 0.05 based on Rosetta Resolver analysis for all pairwise treatment comparisons. The fold-change refers to the second intensity over the first.	WBPaper00041939:control_vs_UVC-EtBr-exposed_51h

20 Expression Patterns

• Primary Identifier: Expr4227
• Remark: Reporter gene fusion type not specified.
• Pattern: Expressed in NSM and ADF neurons.

• Primary Identifier: Expr4564
• Pattern: Expression started to increase at the age of day 4 and became three fold at the age of day 9 compared to the young animal (day 2).

• Primary Identifier: Expr2035603
• 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: Expr1162630
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr1796
• Pattern: Expressed in pharynx.

• Primary Identifier: Expr15433

• Primary Identifier: Expr12176
• Pattern: Under normoxic conditions (21% O2), tph-1prom::gfp was robustly expressed in the head of the adult hermaphrodite in the NSM and ADF neurons and was weakly expressed in the ASG sensory neurons of a small percentage (5%; n = 141) of animals.

• Primary Identifier: Expr959
• Remark: Reporter gene fusion type not specified.
• Pattern: Expressed in C. elegans serotonergic neurons: NSM, ADF, hermaphrodite-specific HSN, male-specific CP, and, rarely, AIM and RIH. tph-1::GFP expression in most of these neurons is observed by the L1 stage but expression in the late-maturing HSN and CP neurons is observed in the adult stage.

• Primary Identifier: Expr13882
• Pattern: Single-molecule fluorescent in situ hybridization (smFISH) of endogenous tph-1 mRNA revealed sexually dimorphic expression in ADF neurons.

• Primary Identifier: Expr13884
• Pattern: Under well-fed conditions, a tph-1 fosmid reporter was dimorphically expressed in both NSM and ADF, with L1 males showing higher expression than hermaphrodites.

• Primary Identifier: Expr16000
• Pattern: We next focused on the smallest Cis Regulatory Module, a 99-bp region located upstream the tph-1/tryptophan hydroxylase locus (tph-1prom17); this construct drives gfp expression exclusively in the ADF neuron.

• Primary Identifier: Expr11639
• Pattern: tph-1::gfp was expressed primarily only in the NSM, the ADF, and the adult HSN neurons.

• Primary Identifier: Expr12703
• Pattern: Ptph-1::gfp was robustly expressed in the head of animals in the NSM and ADF neurons, and was not expressed in D neurons.

• Primary Identifier: Expr8142
• Remark: Picture: Figure 1, Figure 2.
• Pattern: Pharyngeal expression of the pTPH-1::GFP reporter is limited to the NSM neurons in larvae and adults; outside the pharynx, expression is also seen in the nerve ring and some other extra-pharyngeal neurons e.g. HSN, ADF. During embryogenesis, expression of pTPH-1::GFP within the pharyngeal primordium can first be observed at approximately 300 min. of development. When the pharyngeal primordium begins to elongate at 2-fold stage, strong expression of the pTPH-1::GFP reporter is observed both in the muscle cells of the procorpus and metacorpus. In the late 3-fold stage, as the pharynx elongates and matures, pharyngeal expression of the pTPH-1::GFP reporter becomes restricted to the NSM neurons; pharyngeal muscle expression weakens and eventually disappears completely by the time of hatching.

• Primary Identifier: Expr8602
• Remark: Picture: Fig. 1. Reporter gene fusion type not specified.
• Pattern: tph-1::gfp expression in the ADF neurons of the dauers was on average 2.8-fold higher than that in their non-dauer siblings. In addition, tph-1::gfp was ectopically induced in the ventral motor neurons in WT dauers as well as in ocr-2 and osm-9 mutant dauers. However, tph-1::gfp expression levels in the NSM neurons were not significantly affected. Furthermore, the increase in tph-1::gfp expression in ADF and the expression in the motor neurons both were diminished within 24 h after the dauers were allowed to recover under optimal growth conditions .

• Primary Identifier: Expr1032731
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr1988
• Remark: This antibody recognize both bas-2 and tph-1, see Expr1235. Worms were prepared differently in Expr1235 and Expr1988 to highlight either hypodermal or neuronal staining.
• Pattern: Observed many worms staining of cell bodies and processes of NSMs, identified as serotonergic neurons in the pharynx. Occasionally saw one or two small cells in the head in the location of other unknown serotonergic neurons. In a few hermaphrodites, identified a cell near the vulva located sublaterally and with a process extending ventrally as HSN. Also stained 6 neurons with processes in the ventral nerve cord, identified as CP neurons. No staining of dopaminergic neurons.
• Subcellular Localization: Neuronal cell bodies and processes.

• Primary Identifier: Marker120
• Pattern: Marker for NSM neurons.

• Primary Identifier: Expr2017464
• 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: Expr1027717
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

38 GO Annotation

9 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00006600
• Start: 7549335
• End: 7551983
• Strand: 1

38 Ontology Annotations

4 Regulates Expr Cluster

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly increased expression in tph-1(mg280) animals comparing to N2 animals.	DESeq2, FDR < 0.01.	WBPaper00059224:tph-1(mg280)_upregulated
	Transcripts that showed significantly increased expression in tph-1(mg280);odIs77 comparing to in odIs77 control animals.	EdgeR, FDR<0.01	WBPaper00060921:tph-1(mg280)_upregulated
	Transcripts that showed significantly decreased expression in tph-1(mg280);odIs77 comparing to in odIs77 control animals.	EdgeR, FDR<0.01	WBPaper00060921:tph-1(mg280)_downregulated
	Transcripts that showed significantly decreased expression in tph-1(mg280) animals comparing to N2 animals.	DESeq2, FDR < 0.01.	WBPaper00059224:tph-1(mg280)_downregulated

1 Sequence

• Length: 2649

1 Sequence Ontology Term

• Name: gene

19 Strains

• WBStrain00027500
• WBStrain00027519
• WBStrain00027113
• WBStrain00029409
• WBStrain00029416
• WBStrain00029415
• WBStrain00029419
• WBStrain00029426
• WBStrain00029425
• WBStrain00029424
• WBStrain00051809
• WBStrain00055118
• WBStrain00055121
• WBStrain00061887
• WBStrain00062895
• WBStrain00007901
• WBStrain00006655
• WBStrain00007909
• WBStrain00007903

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrII_7548145..7549334
• Length (nt): 1190
• Chromosome Location: II: 7548145-7549334
• Organism: Caenorhabditis elegans