WormFlux: mechanistic analysis of C. elegans metabolism

Gene Overview

Name .....................................................	:	dpyd-1
Sequence ID .....................................................	:	C25F6.3
Status (?) Can be one of the following two: Curated (manually annotated or based on a curated SACURE result), or Not curated (SACURE result reported without manual check). .....................................................	:	Curated
KO (?) The KEGG orthology group (KO) that is associated with this gene. .....................................................	:	K00207DPYD; dihydropyrimidine dehydrogenase (NADP+) [EC:1.3.1.2]
Enzymes in the model (?) Enzymes that are part of the current metabolic network model. .....................................................	:	1.3.1.2names: dihydropyrimidine dehydrogenase (NADP+);dihydrothymine dehydrogenase;dihydrouracil dehydrogenase (NADP+);4,5-dihydrothymine: oxidoreductase;DPD;DHPDH;dehydrogenase, dihydrouracil (nicotinamide adenine dinucleotide phosphate);DHU dehydrogenase;hydropyrimidine dehydrogenase;dihydropyrimidine dehydrogenase (NADP)
Other enzymes (?) Enzymes that are associated with this gene in the WormFlux database, but not included in the current network model. .....................................................	:	None
Model reactions (?) Reactions that are part of the current metabolic network model. See the bottom of this page for a table of reactions. .....................................................	:	RC00978, RC01415
Relevant model reactions (?) Model reactions that follow from the KEGG reactions associated with this gene, but that exclude this gene due to differences in reaction specificity or localization compared to the predictions for this gene. .....................................................	:	ERROR
Other reactions (?) KEGG reactions that are associated with this gene in the WormFlux database, but not included in the current network model. .....................................................	:	R08226

In WormPaths (?) Pathway maps where this gene is represented are listed here. .....................................................	:	Pyrimidine metabolism

External links

WBGene00016103

CELE_C25F6.3

Q18164

► | Gene-KO-Enzyme-Reaction Associations (click to view)▼ | Gene-KO-Enzyme-Reaction Associations (click to hide)

SACURE (?) Associations established by SACURE (Systematic Annotation by CUration and REgression).

SACURE pipeline annotates genes based on a logistic function that converts evidence from multiple resources into a KEGG orthology decision, which is then associated with enzymes and reactions. False positives and false negatives of the logistic function are separated out during manual curation for making exceptional decisions.

See HELP in the upper menu for a description of the SACURE pipeline.

See below for a summary of association scores from SACURE.

Results (?) KO: Associated KEGG Orthology groups
Enzyme: Associated enzymes in EC numbering
Reactions: Associated reactions from KEGG reaction database.

Confidence level is indicated for each association as a function of overall SACURE score (a probability of true association; see below in the SACURE scores section). Score ranges for HIGH, MEDIUM, and LOW confidence levels are >0.99, 0.90-0.99, and 0.50-0.90, respectively. If an association is accepted with a probability less than 0.50 (due to an exceptional reason), then the confidence level is LOW.

Not determined indicates that annotation analysis resulted in no clear associations.

	ID - Confidence
KO	K00207 - High
Enzyme	1.3.1.2 - High
Reaction	R00978 - High R01415 - High R08226 - High

Comments

Based on the logistic function.
See scores from predictors and the logistic function below (SACURE summary).

Reconstruction (?) Associations established during the reconstruction process by lenient annotation, literature search, or gap-filling.

Results (?) KO: Associated KEGG Orthology groups
Enzyme: Associated enzymes in EC numbering
Reactions: Associated reactions from KEGG reaction database or custom reactions developed during reconstruction.

	ID - Confidence
KO	ERROR
Enzyme	ERROR
Reaction	ERROR

Comments

ERROR

► | SACURE Summary (click to view)▼ | SACURE scores (click to hide)

Score table (?) Association scores for KOs best matching to the query gene according to each annotation predictor, and for the accepted KO if there is any (rightmost columns).

The predictors are ordered in decreasing weight of contribution to the decision-making process in SACURE.

See above for the final decision on the annotation of this gene.

Predictor	Best scoring KOs	Best score	K00207	ERROR
KEGG (?) Score represents the annotation in KEGG database by June 2014. Takes a value of either 0 (KO is not associated with the query gene) or 1 (KO is associated with the query gene).	K00207	1	1	ERROR
Cluster (?) Score represents the degree of relatedness of a KO to the query gene based on the clustering in the phylogenetic tree of protein sequences (see below for the tree). Takes values from 0 to 1.	K00207	1.00	1.00	ERROR
myKEGG (?) Score represents the degree of relatedness of a KO to the query gene based on the Smith-Waterman alignment of protein sequence with most similar sequences from all organisms in the KEGG database. Takes values from 0 to 1. KOunknown indicates the score for sequences without any KO association in KEGG database.	K00207	0.92	0.92	ERROR
Tree (?) Score shows the degree of relatedness of a KO to the query gene based on the density of this KO in the phylogenetic tree of protein sequences (see below for the tree). Takes values from 0 to 2 as the score is normalized to the second best KO. KOunknown indicates the score for sequences without any KO association in KEGG database.	K00207	1.99	1.99	ERROR
KOG (?) Score indicates the absence or presence of a KO in association with one of the orthologs of the query gene according to a eukaryotic orthology database independent of KEGG (see HELP* in the upper menu for details). Takes a value of either 0 (absent) or 1 (present*).	Not applicable	0	0	ERROR
WormBase (?) Score represents matching between the KEGG descriptions of a KO (KO name and all related enzyme names) and the descriptions of the query gene in WormBase (gene overview and protein domains). Value is increased by 0.5 for every perfect word match and reduced by 0.1 for each character interruption. A non-matching word always creates a 0 score. WormBase description used for this gene was: "4Fe-4S ferredoxin, iron-sulphur binding, conserved site $ Aldolase-type TIM barrel $ Dihydroorotate dehydrogenase $ Dihydroorotate dehydrogenase, class 1, core $ Dihydroorotate dehydrogenase, class 1/ 2 $ Dihydrouridine synthase (Dus) $ FAD-dependent pyridine nucleotide-disulphide oxidoreductase $ Fumarate reductase, C-terminal $ NAD(P)-binding $ Pyridine nucleotide-disulphide oxidoreductase $ Pyridine nucleotide-disulphide oxidoreductase, class-II $ tRNA-dihydrouridine synthase $$ dpyd-1 encodes the C. elegans ortholog of human DihydroPYrimidine Dehydrogenase (DPYD), which when mutated leads to thymine-uraciluria (OMIM:274270); DPYD-1 is the first and rate-limiting enzyme for uracil and thymine metabolism to 5,6-dihydrouracil and 5,6-dihydrothymine, respectively, and in humans, functions in metabolism of the anti-cancer pyrimidine antagonist 5-fluorouracil (5-FU); in C. elegans, loss of dpyd-1 activity via RNAi results in sensitivity (decreased survival) to 5-FU while conversely, DPYD-1 overexpression affords increased germ cell survivability to 5-FU."	K05539 K05545 and 5 more...All best scoring KOs: K05539, K05545, K05544, K05541, K05540, K05543, K05542	1.5	1.0	ERROR
Overall (?) Overall score from SACURE that represents the logistic-regression-based probability of acceptance of a KO in association with the query gene.	K00207	1.000	1.000	ERROR

► | Localization scores (click to view)▼ | Localization scores (click to hide)

Score table (?) Localization scores for proteins encoded by the query gene.

Each predictor is used to determine whether the protein is localized to mitochondria or other compartment.

Together with other genes and other predictors, these scores were used in the determination of the subcellular location of reactions associated with the query gene (see below for the reactions).

Predictor	Mitochondrial	Other
Mitoprot (?) Score represents the predicted probability that the protein is targeted to mitochondria (mitochondrial score) or not (other score) according to Mitoprot (click to reach). If multiple isofoms of the same protein are available the highest scores are shown for each compartment.	0.02	0.98
MitoMiner (?) Score evaluates the evidence for mitochondrial targeting based on the orthologs in 12 eukaryotic model organisms that are in the MitoMiner database (click to reach). If clear orthologs for the query gene are available in MitoMiner organisms, the score takes a value between 0 and 1 as a function of the ratio of orthologs that have hits (contributes to the mitochondrial score) or no hits (determines the other score) in the database. Mitochondrial score is also a function of the strength of the evidence for the orthologs found in the database (experimental evidence is given a higher weight than theoretical evidence during scoring).	0.00	1.00
UniProt (?) Score shows the subcellular localization of proteins encoded by this gene as reported in UniProt (click to reach) in October 2014. If a report is available, the score takes a value of either 0 (not reported to be localized to the pertaining compartment) or 1 (reported to be localized to the pertaining compartment).	Not available	Not available
Org. DB (?) Score shows the subcellular localization of proteins encoded by this gene as reported in Organelle Database (click to reach). If a report is available, the score takes a value of either 0 (not reported to be localized to the pertaining compartment) or 1 (reported to be localized to the pertaining compartment).	Not available	Not available

► | Phylogenetic tree (click to view)▼ | Phylogenetic tree (click to hide)

(?) Phylogenetic tree of protein sequences including the query gene, nearest matches in selected organisms from different taxonomic groups, and paralogs in C. elegans. All sequences are obtained from KEGG database.

This figure is interactive, click items to reach relevant KEGG pages.

A low number of orthologs represented on this tree indicates the lack of similar sequences in other organisms.

See below for the legend.

Sequence labels indicate KO, taxonomy or model organism, organism name (if taxonomic group), and gene name, respectively. CEL, C. elegans; HSA, H. sapiens; DME, D. melanogaster; ATH, A. thaliana; SCE, S. cerevisiae; BAC, bacteria; ARC, archaea; PRO, protists; FUN, fungi; PLA, plants; INV, invertebrates; NEM, nematodes; ART, arthropods; VER, vertebrates; MAM, mammals. Parenthetical information for organisms other than CEL indicates whether the genes are introduced as best matches (B) or reciprocal best hits (R) to the query gene. Parenthetical information for CEL indicates whether the genes are introduced as paralogues (P) of the query gene or as reciprocal best matches to one of the other organisms in the tree (B). Organism abbreviations are from KEGG.

Reactions

Enzyme

Reactants

Products

Genes (?) Multiple genes are separated by OR (I) or AND (&).

I indicates that genes are redundant within the group (e.g. paralogs encoding the same enzyme).
& indicates that genes are non-redundant within the group (e.g. genes encoding different subunits of the same enzyme).

If there are multiple groups of genes, as in an enzyme complex with some enzymes associated with multiple genes, or in a case where the same enzyme is associated with different orthology groups with paralogs, each group with multiple genes is shown in parentheses.

Pathway

RC00978Name: 5,6-Dihydrouracil:NADP+ oxidoreductase Type: Regular Location: Cytosol KEGG ID: R00978 click to see details on this item	1.3.1.2Name: dihydropyrimidine dehydrogenase (NADP+) Other names: dihydrothymine dehydrogenase, dihydrouracil dehydrogenase (NADP+), 4,5-dihydrothymine: oxidoreductase, DPD, DHPDH, dehydrogenase, dihydrouracil (nicotinamide adenine dinucleotide phosphate), DHU dehydrogenase, hydropyrimidine dehydrogenase, dihydropyrimidine dehydrogenase (NADP) click to see details on this item	[c] : 56duraName: "5,6-dihydrouracil" Formula: C4H6N2O2 Charge: 0 click to see details on this item + nadpName: Nicotinamide adenine dinucleotide phosphate Formula: C21H25N7O17P3 Charge: -3 click to see details on this item		hName: H+ Formula: H Charge: 1 click to see details on this item + nadphName: Nicotinamide adenine dinucleotide phosphate - reduced Formula: C21H26N7O17P3 Charge: -4 click to see details on this item + uraName: Uracil Formula: C4H4N2O2 Charge: 0 click to see details on this item	dpyd-1	Pyrimidine metabolism
RC01415Name: 5,6-Dihydrothymine:NADP+ oxidoreductase Type: Regular Location: Cytosol KEGG ID: R01415 click to see details on this item	1.3.1.2Name: dihydropyrimidine dehydrogenase (NADP+) Other names: dihydrothymine dehydrogenase, dihydrouracil dehydrogenase (NADP+), 4,5-dihydrothymine: oxidoreductase, DPD, DHPDH, dehydrogenase, dihydrouracil (nicotinamide adenine dinucleotide phosphate), DHU dehydrogenase, hydropyrimidine dehydrogenase, dihydropyrimidine dehydrogenase (NADP) click to see details on this item	[c] : 56dthmName: "5,6-Dihydrothymine" Formula: C5H8N2O2 Charge: 0 click to see details on this item + nadpName: Nicotinamide adenine dinucleotide phosphate Formula: C21H25N7O17P3 Charge: -3 click to see details on this item		hName: H+ Formula: H Charge: 1 click to see details on this item + nadphName: Nicotinamide adenine dinucleotide phosphate - reduced Formula: C21H26N7O17P3 Charge: -4 click to see details on this item + thymName: Thymine Formula: C5H6N2O2 Charge: 0 click to see details on this item	dpyd-1	Pyrimidine metabolism

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