GPR curation for subsystems related to amino acid metabolism

[JHL-452b]

Current behavior:

15 genes are discovered to be uncorrelated with their corresponding reactions about subsystems of amino acid metabolism.

Gene	UniProtID	Reaction	Subsystem	GPR	Correlation	Manually check
ENSG00000134333	P00338	MAR04287: H2O + NADP+ + succinate semialdehyde --> 2.0 H+ + NADPH + succinate	Alanine, aspartate and glutamate metabolism	ENSG00000134333	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. According to the annotation, the gene ENSG00000134333 encodes an enzyme that catalyzes the interconversion of pyruvate and lactate with the concomitant interconversion of NADH and NAD(+), not the conversion involving H2O, NADP+, succinate semialdehyde, H+, NADPH, and succinate. Therefore, the specified gene does not catalyze the provided reaction.	No
ENSG00000133048	P36222	MAR08375: chitin-component + H2O --> N-acetylglucosamine	Amino sugar and nucleotide sugar metabolism	ENSG00000111261 or ENSG00000133048 or ENSG00000133063 or ENSG00000134216	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000133048 encodes a carbohydrate-binding lectin with a preference for chitin but has no chitinase activity. The reaction provided involves the hydrolysis of a chitin component to produce N-acetylglucosamine, which requires chitinase activity. Since the gene product lacks this enzymatic function, it cannot catalyze the reaction, making the gene irrelevant to the reaction described.	No
ENSG00000159423	P30038	MAR00088: 3-amino-propanal + H2O + NAD+ --> beta-alanine + 2.0 H+ + NADH	Beta-alanine metabolism	ENSG00000111275 or ENSG00000137124 or ENSG00000159423	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000159423 encodes for an enzyme that catalyzes the conversion of delta-1-pyrroline-5-carboxylate to glutamate, which is a step in the urea and tricarboxylic acid cycles. The described catalytic activity involves substrates such as L-glutamate 5-semialdehyde and results in the production of L-glutamate and NADH. However, the reaction provided involves the conversion of 3-amino-propanal to beta-alanine, which is not mentioned in the gene's annotated function or catalytic activity. Therefore, the gene is not relevant to the reaction provided.	No
ENSG00000181652	Q674R7	MAR03995: cystine + H+ + NADPH <=> 2.0 cysteine + NADP+	Cysteine and methionine metabolism	ENSG00000181652 or ENSG00000184470 or ENSG00000197763 or ENSG00000198431	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000181652 encodes a protein involved in phospholipid scrambling and autophagosomal membrane expansion, facilitating the movement of specific phospholipids across membranes. In contrast, the reaction provided involves the reduction of cystine to cysteine using NADPH, which is unrelated to the gene's described functions.	No
ENSG00000104951	Q96RQ9	MAR05390: H2O + methionine + O2 --> 4-methylthio-2-oxobutanoic acid + H+ + H2O2 + NH3	Cysteine and methionine metabolism	ENSG00000104951	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000104951 encodes for a secreted L-amino-acid oxidase that primarily converts L-aromatic amino acids like phenylalanine, tyrosine, and tryptophan to their respective keto acids, along with weak L-arginine oxidase activity. The enzyme's activity includes the production of H2O2 and NH4(+). However, the provided reaction involves the oxidative deamination of methionine to 4-methylthio-2-oxobutanoic acid, which is not mentioned among the substrates for the gene's annotated enzymatic activities. Therefore, the gene's function does not align with the given reaction involving methionine.	No Yes
ENSG00000165672	P30048	MAR04120: 2.0 GSH + H2O2 --> GSSG + 2.0 H2O	Glutathione metabolism	ENSG00000116157 or ENSG00000117450 or ENSG00000117592 or ENSG00000126432 or ENSG00000164294 or ENSG00000165672 or ENSG00000167468 or ENSG00000167815 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000165672 encodes for a thiol-specific peroxidase, which catalyzes the reduction of hydroperoxides using thioredoxin as a substrate, resulting in the production of alcohols and water. The catalyzed reaction specifically involves [thioredoxin]-dithiol and a hydroperoxide to form [thioredoxin]-disulfide, alcohol, and water. However, the reaction provided involves the reduction of hydrogen peroxide using glutathione (GSH) to produce glutathione disulfide (GSSG) and water, which is a different biochemical pathway. Therefore, the gene ENSG00000165672 and the provided reaction are not related.	No
ENSG00000166562	Q9BY50	MAR06978: [protein]-N6,N6,N6-trimethyl-L-lysine + H2O --> [protein] + H+ + N6,N6,N6-trimethyl-L-lysine	Lysine metabolism	ENSG00000114902 and ENSG00000118363 and ENSG00000129128 and ENSG00000140612 and ENSG00000166562	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000166562 encodes for a protein that functions as a catalytic component of the signal peptidase complex (SPC), which is responsible for cleaving N-terminal signal sequences from nascent proteins as they are translocated into the endoplasmic reticulum. The specific catalytic activity involves the cleavage of hydrophobic N-terminal signal peptides. In contrast, the reaction provided involves the cleavage of [protein]-N6,N6,N6-trimethyl-L-lysine, which does not match the described function of the gene. Therefore, the gene and the reaction are not related.	Yes
ENSG00000140612	P67812	MAR06978: [protein]-N6,N6,N6-trimethyl-L-lysine + H2O --> [protein] + H+ + N6,N6,N6-trimethyl-L-lysine	Lysine metabolism	ENSG00000114902 and ENSG00000118363 and ENSG00000129128 and ENSG00000140612 and ENSG00000166562	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000140612 encodes a protein that functions as a catalytic component of the signal peptidase complex (SPC), which is involved in cleaving N-terminal signal sequences from nascent proteins being translocated into the endoplasmic reticulum. The described function and catalytic activity pertain to the cleavage of hydrophobic N-terminal signal peptides. However, the provided reaction involves the cleavage of N6,N6,N6-trimethyl-L-lysine from a protein, a process unrelated to the gene's annotated function.	Yes
ENSG00000166562	Q9BY50	MAR08029: [protein]-N6,N6,N6-trimethyl-L-lysine + H2O --> [protein] + H+ + N6,N6,N6-trimethyl-L-lysine	Lysine metabolism	ENSG00000114902 and ENSG00000118363 and ENSG00000129128 and ENSG00000140612 and ENSG00000166562	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000166562 encodes a component of the signal peptidase complex (SPC), which cleaves N-terminal signal sequences from nascent proteins as they are translocated into the endoplasmic reticulum. The reaction provided involves the cleavage of N6,N6,N6-trimethyl-L-lysine from a protein, which is not an N-terminal signal seq. Therefore, the gene does not relate to the reaction described.	Yes
ENSG00000138801	O43252	MAR07128: ATP + H+ + selenate --> adenylylselenate + PPi	Metabolism of other amino acids	ENSG00000138801 or ENSG00000198682	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000138801 has bifunctional ATP sulfurylase and APS kinase activities, which are involved in the sulfate activation pathway. Specifically, it mediates the conversion of sulfate to adenosine 5'-phosphosulfate (APS) and subsequently to 3'-phosphoadenylylsulfate (PAPS). However, the reaction provided involves ATP and selenate forming adenylylselenate and PPi, which is not related to the sulfate activation pathway or the activities of ATP sulfurylase and APS kinase associated with the gene ENSG00000138801.	No
ENSG00000198682	O95340	MAR07128: ATP + H+ + selenate --> adenylylselenate + PPi	Metabolism of other amino acids	ENSG00000138801 or ENSG00000198682	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000198682 encodes an enzyme with bifunctional ATP sulfurylase and APS kinase activities, involved specifically in the sulfate activation pathway, converting sulfate to adenosine 5'-phosphosulfate (APS) and subsequently to 3'-phosphoadenylylsulfate (PAPS). The reaction provided involves ATP, H+, and selenate, yielding adenylylselenate and PPi, which is not related to sulfate metabolism. Therefore, the enzyme encoded by this gene does not participate in the reaction involving selenate.	No
ENSG00000165996	B0YJ81	MAR05288: 349.0 ATP + glycogenin + 698.0 H2O --> 349.0 ADP + 22.0 alanine + 12.0 arginine + 12.0 asparagine + 26.0 aspartate + 6.0 cysteine + 15.0 glutamate + 14.0 glutamine + 18.0 glycine + 360.0 H+ + 9.0 histidine + 12.0 isoleucine + 39.0 leucine + 18.0 lysine + 8.0 methionine + 20.0 phenylalanine + 349.0 Pi + 15.0 proline + 31.0 serine + 25.0 threonine + 7.0 tryptophan + 13.0 tyrosine + 28.0 valine	Protein degradation	ENSG00000165996 or ENSG00000206527	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000165996 is involved in the catalysis of the dehydration of 3-hydroxyacyl-CoA into trans-2,3-enoyl-CoA during the long-chain fatty acids elongation cycle, whereas the provided reaction involves the conversion of ATP and glycogenin to ADP and various amino acids. The functions of the gene do not overlap with the biochemical processes described in the reaction, which pertains to amino acid synthesis and not fatty acid elongation.	No
ENSG00000206527	Q6Y1H2	MAR05288: 349.0 ATP + glycogenin + 698.0 H2O --> 349.0 ADP + 22.0 alanine + 12.0 arginine + 12.0 asparagine + 26.0 aspartate + 6.0 cysteine + 15.0 glutamate + 14.0 glutamine + 18.0 glycine + 360.0 H+ + 9.0 histidine + 12.0 isoleucine + 39.0 leucine + 18.0 lysine + 8.0 methionine + 20.0 phenylalanine + 349.0 Pi + 15.0 proline + 31.0 serine + 25.0 threonine + 7.0 tryptophan + 13.0 tyrosine + 28.0 valine	Protein degradation	ENSG00000165996 or ENSG00000206527	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000206527 codes for an enzyme that catalyzes the dehydration of 3-hydroxyacyl-CoA intermediates into trans-2,3-enoyl-CoA as part of the elongation cycle of very long-chain fatty acids (VLCFAs). This process is involved in the elongation of lipid chains by adding two carbons in each cycle and occurs in the endoplasmic reticulum. The provided reaction, however, involves the hydrolysis of ATP and the synthesis of various amino acids from glycogenin, which is unrelated to the catalytic function of the gene product. Therefore, based on the annotation of the gene, there is no connection between the gene's function in lipid elongation and the amino acid synthesis reaction provided.	No
ENSG00000128683	Q99259	MAR04174: aspartate + H+ --> beta-alanine + CO2	Beta-alanine metabolism	ENSG00000128683 or ENSG00000136750	Pending No, the gene is not relevant to the reaction provided. Analysis: The gene ENSG00000128683 catalyzes the synthesis of gamma-aminobutyric acid (GABA) from L-glutamate with the release of CO2, indicated by references to PubMed:10671565 and PubMed:17384644. The described reaction involves aspartate being converted to beta-alanine with the release of CO2, which differs from the gene's characterized function of converting L-glutamate to GABA. Therefore, the gene and the reaction are unrelated based on the provided annotation.	No
ENSG00000006695	Q12887	MAR05337: GSH + urocanate <=> S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione	Histidine metabolism	ENSG00000006695 or ENSG00000054267 or ENSG00000117682 or ENSG00000120942 or ENSG00000183665	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000006695 encodes an enzyme that converts protoheme IX and farnesyl diphosphate to heme O, whereas the reaction provided involves GSH and urocanate forming S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione. These reactions involve different substrates and products, indicating that the gene's function is unrelated to the specified reaction.	No

[hhl-24]

keep gene ENSG00000104951 for reaction MAR05390，ENSG00000104951 has catalytic activity(an L-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4+)

[JHL-452b]

Indeed, methionine belongs to L-alpha-amino acid and 4-methylthio-2-oxobutanoic acid belongs to a 2-oxocarboxylate. So, the MAR05390 is compatible with the function of ENSG00000104951. Agree to keep ENSG00000104951 for MAR05390.

[JHL-452b]

Fixed by #936