NTR: neutral amino acid, sodium: L-arginine antiporter activity

[Argoudpuy]

Please provide as much information as you can:

• Suggested term label:
  neutral amino acid, sodium: L-arginine antiporter activityy

• Definition (free text)
  Enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: L-arginine(in) + neutral amino acid(out) + Na(+)(out) = L-arginine(out) + neutral amino acid(in) + Na(+)(in).

• **Reference, in format PMID:10903140

• Gene product name and ID to be annotated to this term

• Parent term(s)
  solute:cation antiporter activity

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

[hdrabkin]

trying to find a CHEBI id for 'neutral amino acid' to see if I can find a RHEA or if I can request one.

[hdrabkin]

Neutral amino acids are the amino acids that possess an equal number of amino and carboxylic acid groups. The groups attached to the amino acid, apart from the carboxylic acid groups and amino acid groups, may be either polar or non-polar.
note this def has to be pH dependent; in GO we use the form that exists at pH 7.3
I thought maybe 'non-polar amino acid', but

non-polar amino acids; CHEBI:25588
Nonpolar amino acids include alanine (Ala), leucine (Leu), isoleucine (Ile), proline (Pro), tryptophan (Trp), valine (Val), phenylalanine (Phe), and methionine (Met). The side chains of these amino acids are long carbon chains or carbon rings,

[hdrabkin]

So I'm thinking Neutral amino acids at pH 7.3, the R group would have no charge?
@amorgat does RHEA have a 'neutral amino acid' entry? I might not be searching correctly

[deustp01]

I think "neutral" would be all of the nonpolar ones plus glutamine, asparagine, serine, threonine, and cysteine - uncharged at pH 7.3 but polar side chains.
Question: does the transporter studied in PMID: 10903140 really interact roughly equally with this full range of amino acids, and if not, do you need to find a grouping term for the full range of neutral amino acids to deal with this term request, or only one to cover the range shown in the paper?
But you'd still need a grouping term for the subset that this transporter does handle, so my evasion may not help.

[deustp01]

Or maybe here multiple annotations are needed. By analogy, Human ALDOB can convert fructose 1,6-bisphosphate to glyceraldehyde 3-phosphate + dihydroxyacetone phosphate fructose-bisphosphate aldolase activity and can also convert fructose 1-phosphate to glyceraldehyde + dihydroxyacetone phosphate
fructose-1-phosphate aldolase activity - one gene product, 2 activities, 2 GO terms, and no attempt in GO to make a grouping term to merge them into a single annotation.

[hdrabkin]

I'm also thinking of multiple annotations to whatever specific amino acid might do.

[Argoudpuy]

Hi,
I hesitated to ask a new term GO for each amino acid for which a Rhea has been created from this PMID:10903140, namely L-leucine[Rhea:70831], L-glutamine[Rhea:70835], L-histidine[Rhea:70839] and L-cysteine[Rhea:70847].
Finally SLC7A6 transports very specific amino acid, it is not a SLC transporter with a large spectre, probably better to create a specific term for each amino acid describes above.
I hope that helps

[hdrabkin]

So, I will create the term, and define 'neutral amino acid' based on the def above (Neutral amino acids are the amino acids that possess an equal number of amino and carboxylic acid groups.)
taken from https://byjus.com/question-answer/give-an-example-of-neutral-amino-acid/
Therefore, apart from the carboxylic acid and amino acid groups, the groups linked to the amino acid might be non-polar or polar. (
but needs to be pH7.3-friendly, so thinking ahead for future children.
So at 7.3, zwitterionic forms for glycine, tyr, phe, ser, thr, leu, ile, val

[pgaudet]

• Also need to remove the LD from GO:0140893 neutral amino acid, sodium:proton antiporter activity since this is not defining a neutral amino acid

[Argoudpuy]

Hi Harold,
ok but finally according to your definition of a neutral amino acid, this tem will only match L-leucine[Rhea:70831], so it will miss me the 3 others L-glutamine[Rhea:70835], L-histidine[Rhea:70839] and L-cysteine[Rhea:70847].
It's probably better to create a term for each amino acid describes above, what do you think?
thanks

[pgaudet]

@Argoudpuy - histidine is not neutral, is it?

Also, where do they show that this transporter transports cysteine in the paper you cite? I could only find an inhibition assay; is that the antiport assay? It seems the main substrate is arginine, see last sentence of abstract; "These results indicated that arginine has the highest affinity for the intracellular binding site and that arginine release may be the main physiological function of this transporter" - in GO this is all we would capture, ie the main physiological function of the protein.

Looking at other papers for Lat2, it seems to be a broad specificity amino acid antiporter ? against which solute is not clear, in some papers they call this protein (lat2) Na-independent symporter, see https://pubmed.ncbi.nlm.nih.gov/33001560/

Thanks, Pascale