TYMP and PNP GPRs

[juliette-cooke]

I am working on a knockout of the TYMP gene in Human 1, which codes for the TMDPP enzyme. However, the knockout has no effect on any reactions due to its GPR.

Current behavior:

1. Knocking out the TYMP gene in Human 1 has no effect on the TMDPP (MAR04485) reaction because it shares the GPR with the PNP gene.

2. The TYMP gene is also part of the GPRs of 3 other reactions shared with PNP: MAR04709 MAR04695 MAR04603. This may need extra checking but based on Recon3D (see below) and the UniProt pages for TYMP and PNP, TYMP should not be in the GPRs of these 3 reactions.

Gene name	ENSG	Gene card	Current single knockout effect
TYMP	ENSG00000025708	TYMP	None
PNP	ENSG00000198805	PNP	MAR08791 MAR08486 MAR04663 MAR04662 MAR04651 MAR04574

Metabolic Atlas viewer:
TYMP
PNP

Expected feature/value/output:

The TYMP gene should only code for MAR04485, and all the other reactions linked to PNP and TYMP should only be PNP. This is the case in Recon3D for example (see below).

Gene name	ENSG	Gene card	Expected single knockout effect
TYMP	ENSG00000025708	TYMP	MAR04485
PNP	ENSG00000198805	PNP	MAR08791 MAR08486 MAR04709 MAR04695 MAR04663 MAR04662 MAR04651 MAR04603 MAR04574

Recon3D

TYMP
PNP

[haowang-bioinfo]

@juliette-cooke thanks, will check this out

[haowang-bioinfo]

based on Recon3D (see below) and the UniProt pages for TYMP and PNP, TYMP should not be in the GPRs of these 3 reactions.

Yes, the Uniprot annotation does shows that TYMP should not be in the GPRs of MAR04709, MAR04695, MAR04603. Can you please go ahead to make the changes you proposed @juliette-cooke ?

[haowang-bioinfo]

After taking away MAR04485 (#499), 9 reactions are now catalyzed by PNP, which actually is know to interact only with substrates inosine (MAR04574), hypoxanthine (MAR04709), guanosine (MAR04651), guanine (MAR04603), adenosine (MAR08486), and adenine (MAR04695).

This leaves a question about the validity of the other reactions MAR04662 (nicotinate D-ribonucleoside), MAR04663 (xanthosine), MAR08791 (nicotinamide ribonucleoside). Should these reactions be removed or kept?

[haowang-bioinfo]

This leaves a question about the validity of the other reactions MAR04662 (nicotinate D-ribonucleoside), MAR04663 (xanthosine), MAR08791 (nicotinamide ribonucleoside). Should these reactions be removed or kept?

The reaction MAR04663 is supported by this reference, but no experimental evidence found with MAR04662 and MAR8791.