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GPR curation for Propanoate metabolism #844

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JHL-452b opened this issue Sep 22, 2024 · 2 comments
Closed

GPR curation for Propanoate metabolism #844

JHL-452b opened this issue Sep 22, 2024 · 2 comments

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@JHL-452b
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Current behavior:

8 genes are discovered to be uncorrelated with their corresponding reactions in Propanoate metabolism.

Gene UniProtID Reaction GPR Correlation Manually check
ENSG00000116133 Q15392 MAR04497: hydracrylate + NAD+ --> 3-oxopropanoate + H+ + NADH ENSG00000116133 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000116133 is involved in the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. Its known catalytic activities involve cholesterol, desmosterol, lanosterol, and related sterol intermediates, converting them in the presence of NADPH and NADP+. However, the provided reaction involves hydracrylate and NAD+ converting to 3-oxopropanoate, H+, and NADH, which does not involve any sterol intermediates or the same cofactors that the gene product acts upon. Thus, the gene is not relevant to this particular reaction. No
ENSG00000121039 Q8IZV5 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000121039 encodes a retinol dehydrogenase that catalyzes the oxidation of all-trans-retinol to all-trans-retinal, specifically using NADP+ as a cofactor. The reaction described involves 3-hydroxypropionyl-CoA converting to 3-oxopropionyl-CoA with the reduction of NADP+ to NADPH. This reaction is unrelated to the gene product's specified activity of converting all-trans-retinol to all-trans-retinal, thus indicating no relevance between the gene and the reaction provided. No
ENSG00000176387 P80365 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000176387 encodes a protein that catalyzes the conversion of 11beta-hydroxysteroids to 11-oxosteroids and other related reactions involving glucocorticoids and androgens, typically requiring NAD(+) as a cofactor. The reaction provided involves the conversion of 3-hydroxypropionyl-CoA to 3-oxopropionyl-CoA using NADP+ as a cofactor, which is not within the scope of the enzymatic activities described for the gene product. Therefore, the gene and the reaction are unrelated. No
ENSG00000170786 Q8N3Y7 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000170786 encodes an oxidoreductase enzyme that shows activity with all-trans-retinol and NAD(+), converting it to all-trans-retinaldehyde and NADH. This reaction does not involve the substrates 3-hydroxypropionyl-CoA or NADP+ as described in the provided reaction. Therefore, based on the gene's function and catalytic activity, it is not relevant to the reaction involving 3-hydroxypropionyl-CoA and NADP+. No
ENSG00000187134 Q04828 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000187134 encodes a cytosolic aldo-keto reductase involved in the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. It primarily functions in the metabolism of hormones like estrogens and androgens and has broad positional specificity in its actions on steroids. However, the reaction provided involves the conversion of 3-hydroxypropionyl-CoA and NADP+ to H+, NADPH, and 3-oxopropionyl-CoA, which does not align with the gene's annotated function of steroid metabolism. Therefore, the gene does not relate to the given reaction. No
ENSG00000087076 Q9BPX1 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000087076 encodes an enzyme with NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity, which catalyzes the conversion of oestradiol to oestrone and androst-5-en-3beta,17beta-diol to 3beta-hydroxyandrost-5-en-17-one. The reaction provided involves 3-hydroxypropionyl-CoA and NADP+ converting to H+, NADPH, and 3-oxopropionyl-CoA. This reaction is unrelated to the enzyme functions of the gene, which do not involve 3-hydroxypropionyl-CoA, NADP+, or similar substrates. No
ENSG00000160439 Q8NBN7 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000160439 encodes for a retinol dehydrogenase that primarily catalyzes the reaction converting all-trans-retinol to all-trans-retinal using NADP+, while the reaction provided involves 3-hydroxypropionyl-CoA converting to 3-oxopropionyl-CoA with NADP+ as a cofactor. These reactions involve different substrates and products, indicating the gene's enzymatic activity is not related to the provided reaction. No
ENSG00000099377 Q9H2F3 MAR09804: 3-hydroxypropionyl-CoA + NADP+ <=> H+ + NADPH + 3-oxopropionyl-CoA ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000099377 codes for an enzyme involved in the biosynthesis of hormonal steroids and bile acid synthesis, specifically catalyzing reactions involving hydroxylated sterols and various forms of dihydroxycholesterol. It mediates these reactions using NAD+ as a cofactor and is not involved in the metabolism of 3-hydroxypropionyl-CoA or the conversion of NADP+ to NADPH, which is outlined in the provided reaction. No
@feiranl
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feiranl commented Sep 25, 2024

LGTM! Please go ahead to make changes. In summary, several lipid related genes were mis-annotated to the propanoate metabolism. We removed the wrong multiple isoenzymes for those rxns.

@JHL-452b
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Fixed by #884

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