Transport and synthesis of PAPS (R-HSA-174362)

[ukemi]

• [x] Create mouse model
• [x] Do we want to split out the two transporter activities from the biosynthesis in Reactome? I did in mouse. Yes - done by putting metabolism BP terms on reactions R-HSA-174392 and -174389 and transport process terms on R-HSA-427555 and -741449 and removing the metabolism BP term from the parent pathway R-HSA-174362.
• [x] Does PAPSS1 function in the cytosol? PMID:10657990 shows it localizes to the nucleus. PMID:22242175 shows them both places. PAPPS2 may be the key player. For the mouse model I went with an 'evidence for' strategy and included both PAPPS1 and 2 as is done in Reactome. I wish there was a mutant in PAPSS1 that showed a GAG phenotype. PD - here's we're putting the activity in the context of synthesis of sulfated proteoglycans, which is definitely a cytosolic / Golgi-localized activity, so I'm inclined (based on this reasoning, not any additional papers with data) to focus on the cytoplasmic location of the enzyme (for which there is evidence, after all) and ignore the nuclear location (for which there is also evidence).
• [x] Mouse model made production.
• [x] Check Reactome reactions for stoichiometry and charged molecules - OK
• [x] Check mapping of Reactome reactions to Rhea - two items fixed RHEA:28574 shows one proton per sulfate - how can this be electroneutral (R-HSA-427555 has two? But a deeper problem (pretending that I understand ion transport is that PMID: 20219950 appears to be showing that SLC26A2 (and by similarity SLC26A1 exchanges SO4(2-) for Cl(-), so there would be no protons involved at all, but two chloride ions moving in the opposite direction to one sulfate ion. Pending expert advice, we leave this can of worms alone! Reaction R-HSA-174392 is missing an input proton (RHEA:18134) Reaction R-HSA-174389 is missing an output proton (RHEA:24153)
• [x] Mark human pathway as revised (by PD) and re-reviewed (by DPH) @ukemi we should add this item to curation checklist tickets routinely - maybe a good housekeeping practice would be for me to do it one ticket at a time when the Reactome pathways are verified or corrected.

[deustp01]

If the evasions on cytosol / nucleus and on the correct stoichiometry of the sulfate uptake reaction a=are OK, then this item is finished and the ticket can be closed.