Ca2+ ATPases

[ina999111]

I think the reactions describing Ca2+ ATPases should be modified.

Current behavior:

The three Ca2+ ATPases are:

name	abbreviation	from [c] to…	genes
Plasma membrane Ca2+ ATPase	PMCA	[e]	ATP2B1-4
Sarcoplasmic reticulum Ca2+ ATPase	SERCA	[s]	ATP2A1-3
Secretory Pathway Ca2+ ATPase	SPCA	[g]	ATP2C1-2

Currently, the reactions in the model to describe the Ca2+ ATPases are:

id	formula	GPR
MAR00119	ATP[c] + Ca2+[c] + H2O[c] --> ADP[c] + Ca2+[e] + H+[e] + Pi[c]	ATP2B4 or ATP2B3 or ATP2B1 or ATP2B2
MAR07629	ATP[c] + 2.0 Ca2+[c] + H2O[c] --> ADP[c] + 2.0 Ca2+[e] + H+[c] + Pi[c]	ATP2C1 or ATP2B4 or ATP2C2 or ATP2B3 or ATP2B1 or ATP2A3 or ATP2B2 or ATP2A2 or ATP2A1

From the GPR and the formula, MAR00119 seems to accurately describe Plasma membrane Ca2+ ATPase.
However, MAR07629 has the GPR of all Ca2+ ATPases combined.

Expected feature/value/output:

I suggest removing MAR07629 and adding reactions specific to the Sarcoplasmic reticulum Ca2+ ATPase and the Secretory Pathway Ca2+ ATPase.
These would look like:

name	formula	gpr name	gpr ensembl ids
Sarcoplasmic reticulum Ca2+ ATPase	ATP[c] + 2.0 Ca2+[c] + H2O[c] --> ADP[c] + 2.0 Ca2+[s] + H+[c] + Pi[c]	ATP2A1 or ATP2A2 or ATP2A3	ENSG00000196296 or ENSG00000174437 or ENSG00000074370
Secretory Pathway Ca2+ ATPase	ATP[c] + Ca2+[c] + H2O[c] --> ADP[c] + Ca2+[g] + H+[c] + Pi[c]	ATP2C1 or ATP2C2	ENSG00000017260 or ENSG00000064270

This would also require adding the metabolites Ca2+[g] and Ca2+[s] (therefore creating a [s] compartment).

Sources:
10.1016/j.bbamcr.2004.08.018
10.1146/annurev.biochem.73.011303.073700
10.1074/jbc.M501026200

[JHL-452b]

It's a really nice suggestion. I agree to remove MAR07629, , but there are some other issues, including:

• The required new metabolites of Ca2+[g] and Ca2+[s] would be deadend in the model since there are no reactions to consume them. So, do you think it is necessary to add some reactions to transport Ca2+[g] and Ca2+[s] to Ca2+[e] to represent the process of exocytosis?
• I don't understand why Ca2+[s] is created instead of Ca2+[r]? Are the Sarcoplasmic reticulum and Endoplasmic reticulum completely different in structure or function?

[ina999111]

To avoid dead end, I would suggest to create reactions to capture the release of Ca2+ from [s] and [g] to [c] since this is also an important biological phenomenon. I think both reactions (Ca2+[s] --> Ca2+[c] and Ca2+[g] --> Ca2+[c]) should have the same GPR: ITPR1 or ITPR2 or ITPR3 or RYR1 or RYR2 or RYR3.

sources:
https://doi.org/10.1159/000350471
doi: 10.1101/cshperspect.a003996
DOI: 10.1016/j.ceca.2009.09.001
https://doi.org/10.1152/physrev.00033.2020

I also first thought that the sarcoplasmic reticulum was only the "muscle version" of the endoplasmic reticulum, but it turns out that they are distinct organelles that co-exist in muscle cells. (https://doi.org/10.1016/j.tcb.2009.03.006)