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GO:1901243 methionine transmembrane-transporting ATPase activity #10591

Closed gocentral closed 9 years ago

gocentral commented 11 years ago

The definition of GO:1901243 methionine transmembrane-transporting ATPase activity is: "Catalysis of the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: ATP + H2O + methionine(in) = ADP + phosphate + methionine(out).

My question: 'My' current complex transports methionine into the cell, into the opposite direction to the specific reaction mentioned above. However, the first part of the definition is direction-neutral? Do you want to make the stated reaction an example or add a new term for the inward transport reaction?

Thanks, Birgit

PS: I haven't yet made the term for the new complex. I will add the ID to this ticket when I have!

Reported by: bmeldal

Original Ticket: geneontology/ontology-requests/10396

gocentral commented 11 years ago

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Related complex is GO:1990197 methionine transporter complex, just added to TG FF

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Hi Birgit, thanks for waiting.

The '=' sign in the def. of GO:1901243 (and all other reactions in GO) means exactly that - direction-neutral. The strategy in GO is to add the bidirectional reaction term first, and then add inward and/or outward children if necessary. E.g., if you look at descendants of GO:1901243, you'll see that 'D-methionine-transporting ATPase activity' is direction-neutral, and it's got two children for 'D-methionine-exporting ATPase activity' and 'D-methionine-importing ATPase activity'.

Does the paper you were looking at for your bacterial complex term GO:1990197 (http://www.ncbi.nlm.nih.gov/pubmed/?term=22095702) state whether it's indeed D-methionine that's being transported? Or do you have reasons to believe that in your specific case, it could only be D-methionine indeed? (Quoting from a couple of Wikipedia entries: "In nature, only one enantiomer of most chiral biological compounds, such as amino acids (except glycine, which is achiral), is present." "[amino acids] are all L-stereoisomers ("left-handed" isomers) although a few D-amino acids ("right-handed") occur in bacterial envelopes and some antibiotics." If so, I'll add a logical definition to indicate that 'methionine transporter complex' is capable of 'D-methionine-importing ATPase activity'.

Instead, if the paper gives no indication about the stereoisomer, and/or if you don't know what stereoisomer is used for that function in bacterial species, I'll create a child of GO:1901243 for generic 'methionine-importing ATPase activity' and I'll add a logical definition to indicate that 'methionine transporter complex' is capable of 'methionine-importing ATPase activity'.

I'm not done yet ;-) GO:1990197 methionine transporter complex is not limited to Bacteria right now, only to cellular organisms. Do you know if it has any homologue in Eukaryotes?

Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Hi Paola,

Thank you for the explanation of the '='!

PMID:22095702 does not mention which stereoisomer was used. It does cite 2 papers from 1974 stating that the left- and right-handed isomers are transported. And, according to PMID:18621668, both stereoisomers will be transported but only the left-handed isomer inhibits transport at high concentrations. So, I guess we can add logical definitions for both, the L and D isomer import (but there isn't a term for L import...).

The genes for MetN and MetI only seem to occur in bacteria (quick scan through UniProt). However, most organisms, expect for plants and microbes, cannot synthesis methionine and therefore have to take it from their diet (PMID:9636232). Hence, a functional methionine transmembrane transporter must exist in all animals and fungi (quick pubmed search confirms this for mammals and yeast), but it may be constituted differently in different taxa. And obviously, bacteria are also able to import it (probably when certain constituents of the methionine synthesis pathway are missing).

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Hi Birgit, thanks for your reply.

If both stereoisomers are (or may be) transported, it's best to add a logical definition pointing to import of generic 'methionine'. Actually this prompts another question - you defined 'methionine transporter complex' as being "capable of transporting methionine from the periplasm into the cytoplasm in an ATP-dependent manner". Can this complex ONLY do IMPORT? Is any homolog known to be able to export (from cell or organelle) too? The correct logical definition will depend on this (whether it should point to transport or specifically to import). Also, if the complex only ever does import, we may want to reflect that in the name, or at least add an exact synonym. I hope this makes sense.

As for taxon rules: thanks for looking that up, it's quite a useful summary. However, based on it, if we wish to keep the complex term taxon-agnostic, I think we should edit the definition slightly: from the current

"The MetNIQ methionine transporter is member of the group of bacterial ATP-binding cassette (ABC) transporter complexes, and consists of the dimeric ATPase subunit MetN located at the cytoplasmic side of the plasma membrane and the dimeric transmembrane subunit MetI. MetQ is regarded as the periplasmic methionine-binding chaperon subunit. It is capable of transporting methionine from the periplasm into the cytoplasm in an ATP-dependent manner."

to

"An ATP-binding cassette (ABC) transporter complex capable of transporting methionine. An example is the bacterial MetNIQ methionine transporter complex, consisting of the dimeric ATPase subunit MetN located at the cytoplasmic side of the plasma membrane and the dimeric transmembrane subunit MetI. MetQ is regarded as the periplasmic methionine-binding chaperon subunit. The MetNIQ complex is capable of transporting methionine from the periplasm into the cytoplasm in an ATP-dependent manner."

But oh, my head is hurting now... in these complexes, that is not just in your bacterial one, can methionine be transported in non-ATP dependent manner too? If yes, then the logical definition should point to 'methionine transmembrane transporter activity'. If no, then the first sentence in the new def. should read "An ATP-binding cassette (ABC) transporter complex capable of transporting methionine in an ATP-dependent manner" (and the last sentence edited accordingly).

Thanks :-( Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Ok, here it goes:

There is a good introduction in PMID:23748165 (focuses on mosquitoes but compares to all taxa, publ. Aug 2013!)

Options: 1. Create a new term 'methionine (transmembrane?) importer complex' that is both taxon and cofactor agnostic with ALL taxon- and cofactor-specific methionine transporters as DIRECT children and logical definition pointing to a new term 'methionine-importing activity'.

or

2. As above, create a new term 'methionine (transmembrane?) importer complex' that is both taxon and cofactor agnostic,

If we give the taxon- and cofactor-specific complexes separate terms we can then make these also children of other functional complexes, such as the 'GO:0043190 ATP-binding cassette (ABC) transporter complex' in the case of the bacterial MetNIQ complex.

In any case, my term GO:1990197 should probably become: '(bacterial) ATP-binding cassette (ABC) methionine importer complex MetNIQ' (or similar) and be bacterial-specific in its description (if we go to the taxon specific level, opt 2).

I hope I haven't confused you (and myself!) any more!!!

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Hi Birgit,

Back to this... After re-reading all of the info you provide, I think the safest and most conservative option would be to make GO:1990197 'methionine transporter complex' such that:

So I would:

As for the logical definition, I'd have it point to GO:NEW: methionine-importing activity (is_a methionine transmembrane transporter activity, part_of methionine import).

Would you agree? Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Hi Paola,

In your above definition you are keeping the ATP dependence for the complex. In that case the complex name should be something like 'methionine transporter complex, ATP-dependent'.

Or did I miss-read your statements?

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

In my intention, that was only referring to the bacterial example, but if it sounds ambiguous, as it probably does, let's add this at the end of the def:

"... In eukaryotes, methionine import is often Na+ or K+ dependent, rather than ATP-dependent."

And I'd add PMID:23748165 as a dbxref. Hope that sounds better :-) Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

If we define the complex as an 'ATP-binding cassette (ABC) transporter complex' we have added the ATP as an essential part. If you move this reference to the bacterial part:

'An example is the bacterial ATP-binding cassette (ABC) transporter complex MetNIQ methionine transporter...'

it would take the necessity of having ATP out of the main definition.

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

I see your point. Then I'd also delete the link

'methionine importer complex' is_a 'ATP-binding cassette (ABC) transporter complex'

and simply make it is_a protein complex.

Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Yes, definitely delete that link! We could make it

'ATP-binding cassette (ABC) transporter complex' has_part 'methionine importer complex'

Then there is some link which is valid for all those 'methionine importer complexes' that have ATP as the cofactor.

Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Hi Birgit,

I'm afraid I can't add the has_part link you suggest in your latest comment, because that would imply that ALL ATP-binding cassette (ABC) transporter complexes have a methionine importer complex as their integral part, which, to my knowledge, is not correct. No, I'll make a new, generic 'methionine importer complex' term and place GO:1990197 as a child of it, with edited name and def. to reflect the ATP dependency. GO:1990197 can then keep the links it has now. Will do that hopefully tomorrow (have conference call now).

Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Hi Paola,

You are right! Ok, let's go for the 2-step option, then the original, bacterial complex GO:1990197 can have relationships: is_a ATP-binding cassette (ABC) transporter, AND is_a methionine transporter complex.

What are we calling GO:1990197 then? 'methionine transporter complex, ATP-dependent'?

What a headache!

Thanks, Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Started by adding:

[Term] id: GO:1990240 name: methionine-importing activity namespace: molecular_function def: "Catalysis of the transfer of methionine into a cell or organelle, across a membrane." [GOC:pr] synonym: "methionine importer" RELATED [] synonym: "methionine importer activity" EXACT [] synonym: "methionine importing activity" EXACT [] is_a: GO:0043865 ! methionine transmembrane transporter activity relationship: part_of GO:0044690 ! methionine import

More later... thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Then added

[Term] id: GO:1902509 name: methionine-importing complex namespace: cellular_component def: "A protein complex which is capable of methionine-importing activity." [GOC:pr, GOC:TermGenie, PMID:23748165] synonym: "methionine importer complex" EXACT [] synonym: "methionine importing complex" EXACT [] is_a: GO:1902495 {is_inferred="true"} ! transmembrane transporter complex intersection_of: GO:0043234 ! protein complex intersection_of: capable_of GO:1990240 ! methionine-importing activity relationship: capable_of GO:1990240 {is_inferred="true"} ! methionine-importing activity

Nearly there...

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Finally, I edited GO:1990197 'methionine transporter complex'. Now it reads:

[Term] id: GO:1990197 name: ATP-dependent methionine-importing complex namespace: cellular_component def: "An ATP-binding cassette (ABC) transporter complex that is capable of methionine-importing activity. An example is the bacterial MetNIQ methionine transporter, that consists of the dimeric ATPase subunit MetN located at the cytoplasmic side of the plasma membrane and the dimeric transmembrane subunit MetI. MetQ is regarded as the periplasmic methionine-binding chaperon subunit, and is capable of transporting methionine from the periplasm into the cytoplasm in an ATP-dependent manner." [GOC:bhm, PMID:22095702] synonym: "ATP-binding cassette (ABC) methionine importer complex" EXACT [] synonym: "ATP-dependent methionine importer complex" EXACT [] synonym: "ATP-dependent methionine importing complex" EXACT [] synonym: "methionine transport complex" BROAD [] synonym: "methionine transporter" RELATED [] synonym: "methionine transporter complex" BROAD [] synonym: "methionine transporter complex, ATP-dependent" BROAD [] synonym: "MetNI complex" NARROW [] synonym: "MetNI transport complex" NARROW [] synonym: "MetNI transporter" RELATED [] synonym: "MetNI transporter complex" NARROW [] synonym: "MetNIQ complex" NARROW [] synonym: "MetNIQ transport complex" NARROW [] synonym: "MetNIQ transporter" RELATED [] synonym: "MetNIQ transporter complex" RELATED [] is_a: GO:0043190 ! ATP-binding cassette (ABC) transporter complex is_a: GO:1902509 ! methionine-importing complex

I've removed the link is_a 'cation-transporting ATPase complex', because methionine is not a cation ('methionine import' maps to methionine (CHEBI:16811) and this is not a cation, see http://www.ebi.ac.uk/chebi/chebiOntology.do?chebiId=CHEBI:16811)

This should be all :-) Closing this ticket. Have a good weekend! Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Thanks, Paola! Fantastic effort getting it all sorted :)

You have a good weekend, too! Birgit

Original comment by: bmeldal

gocentral commented 11 years ago

Hi,

Do we really want 'catalysis' in this definition ? According to wikipedia, "Catalysis is the increase rate of a chemical reaction due to the participation of a substance called a catalyst." Here we have a transport reaction that is ATP-dependent. The use of catalysis is confusing.

Thanks,

Pascale

Original comment by: pgaudet

gocentral commented 11 years ago

Hi Pascale,

Sorry but I'm no longer sure what term you were referring to...?

Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Original comment by: paolaroncaglia

gocentral commented 11 years ago

I'm closing this ticket. Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 11 years ago

Original comment by: paolaroncaglia