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Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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decision on lipid translocases #14793

Closed ValWood closed 6 months ago

ValWood commented 6 years ago

https://en.wikipedia.org/wiki/Flippase https://www.pombase.org/term/GO:0034203 translocation is currently a type of = transmembrane transport lipid translocation https://www.ebi.ac.uk/QuickGO/term/GO:0034204

The current def fits both from The process in which a solute is transported across a lipid bilayer, from one side of a membrane to the other.

but I think it could be clearer.

This includes transport through the bilayer, or from one side of the bilayer to the other.

Translocation would need to move under "transmembrane transport"

ValWood commented 6 years ago

Follow on from here https://github.com/geneontology/go-ontology/issues/14492 It would be useful to have a MF term to describe "translocases" (flippases)", as a "type" of ~transmembrane~ transporter.

This would house a lot of the "lipid transporter activity" that were identified here: https://github.com/geneontology/go-ontology/issues/14492

pgaudet commented 6 years ago

References PMID: 18439418

ValWood commented 6 years ago

GO:0004012 - phospholipid-translocating ATPase activity GO:0017128 - phospholipid scramblase activity (which appears to be an ATP independent translocating activity)

phosphatidic acid transporter activity- This one is defined like a TM transporter, but it is only used for translocation so far as I can see

Looking at this translocation

It seems that we need a term "lipid translocating activity" to group these? (glycolipid, phospholipid etc)

pgaudet commented 6 years ago

Carried over from #14492

GO ID - Label Annotations Action
GO:1902388 ceramide 1-phosphate transporter activity NOT TM - intermembrane Change label 'intermembrane ceramide 1-phosphate transfer activity'
GO:0035620 ceramide transporter activity Must review annotations - 2 EXP No action yet
GO:0017127 cholesterol transporter activity Must review annotations - mix transporter/carrier 22 EXP No action yet
GO:0017089 glycolipid transporter activity more chaperone Changed label 'intermembrane glycolipid transporter activity'
GO:0034202 glycolipid-translocating activity 3 NOT; 1 EXP Flippase Changed label 'ATPase-coupled intramembrane glycolipid transporter activity'
GO:0034437 glycoprotein transporter activity 2 EXP annotations: one indirect, one possibly endocytosis Obsoleted in #17130
GO:0015648 lipid-linked peptidoglycan transporter activity 3 EXP annotations to 2 proteins, flippases Move to some flippase term
GO:0005319 lipid transporter activity
GO:0042954 lipoprotein transporter activity rather cargo Obsoleted in #17004
GO:0005324 long-chain fatty acid transporter activity
GO:0008525 phosphatidylcholine transporter activity Mix transport - flippase To review
GO:1904121 phosphatidylethanolamine transporter activity Mix transport - flippase To review
GO:0008526 phosphatidylinositol transporter activity all transfer
GO:0005548 phospholipid transporter activity
GO:0008565 protein transporter activity Obsoleted in #17071
GO:0046624 sphingolipid transporter activity Mix transport - flippase To review
GO:0015248 sterol transporter activity Many TM, but others such as P22059 (chaperone?)
pgaudet commented 5 years ago

@ValWood We now have moved flippases under 'intramembrane transporter activity' - does that work for you ?

pgaudet commented 5 years ago

It seems that we need a term "lipid translocating activity" to group these? (glycolipid, phospholipid)

Done

pgaudet commented 5 years ago

Looking at this with @marcfeuermann we propose to add 'flippase' (movement of lipids from the cytosolic to the exoplasmic leaftlet of a membrane) and 'floppase' (movement of lipids from the exoplasmic to the cytosolic of a membrane)

(and move existing terms as children as appropriate, dependent on the direction of the lipid movement).

Would that be OK ? Why are these terms not in GO ? @ukemi @ValWood do you know?

Thanks, Pascale

pgaudet commented 5 years ago

Proposed new terms: +[Term] +id: GO:0140326 +name: ATPase-coupled intramembrane lipid transporter activity +namespace: molecular_function +synonym: "Catalysis of the movement of lipids from one membrane leaflet to the other (lipid flippase activity)." EXACT [PMID:16828084] +is_a: GO:0140303 ! intramembrane lipid transporter activity +created_by: pg +creation_date: 2019-04-29T12:42:26Z + +[Term] +id: GO:0140327 +name: flippase activity +namespace: molecular_function +def: "Catalysis of the movement of lipids from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from ATP hydrolysis to pump the lipid." [PMID:20043909, PMID:25284293, Wikipedia:Flippase] +is_a: GO:0140326 ! ATPase-coupled intramembrane lipid transporter activity +created_by: pg +creation_date: 2019-04-29T12:51:21Z + +[Term] +id: GO:0140328 +name: floppase activity +namespace: molecular_function +def: "Catalysis of the movement of lipids from the cytosolic to the exoplasmic leaftlet of a membrane, using energy from ATP hydrolysis to pump the lipid." [] +is_a: GO:0140326 ! ATPase-coupled intramembrane lipid transporter activity +created_by: pg +creation_date: 2019-04-29T12:58:53Z https://github.com/geneontology/go-ontology/pull/17201

pgaudet commented 5 years ago

https://github.com/geneontology/go-ontology/pull/17201

pgaudet commented 5 years ago

New structure:

ValWood commented 5 years ago

I'm a bit confused about the changes.

Currently GO:0034202 glycolipid-translocating activity broad "flippase activity"

GO:0090555 phosphatidylethanolamine-translocating ATPase activity phosphatidylethanolamine flippase activity | exact

and others...

This ticket is quite confusing anyway though because it dates from the days when "translocation" was merged with "transmembrane transport"

ValWood commented 5 years ago

Looks like you probably dealt with all this https://github.com/geneontology/go-ontology/issues/17186 so reclosing.

Will open new current tickets if I spot any outstanding issues.

pgaudet commented 5 years ago

I apologize about the confusion.

Note that I have removed all flippases activities for floppases. We can create flippases as we find examples.

Thanks, Pascale

ValWood commented 5 years ago

I don't understand how you decided flippase or floppase

https://www.yeastgenome.org/locus/YMR162C#go for example, is flippase

ValWood commented 5 years ago

and https://www.yeastgenome.org/locus/YIL048W

but for some i dont think we know...

pgaudet commented 5 years ago

Hi @ValWood Welcome back !

We looked at this closely with @marcfeuermann and put some comments to help clarify:

However people are quite sloppy with the nomenclature. Most enzymes we looked at are actually floppases, but are called flippases in papers.

We put this comment: "Nomenclature note. Flippases and floppases are ATP-dependent transbilayer lipid translocators. According to an extensively used, though not universal, nomenclature, they catalyze lipid transfer towards the inward monolayer (flippases) or towards the outward monolayer (floppases). Some authors however use the name floppase to denote any enzyme catalyzing transbilayer lipid motion, in some cases even in the absence of ATP requirements. Scramblases are ATP-independent, non-selective, inducing non-specific transbilayer movements across the membrane (PMID 20043909)."

With @marcfeuermann we figured that if the paper doesn't test whether an enzyme flips or flops, then no MF can be assigned.

OK ?

Thanks, Pascale

ValWood commented 5 years ago

OK. I will review ours https://github.com/pombase/curation/issues/2373, there are not many, and let you know if anything is awry.

deustp01 commented 5 years ago

To help curators and users deal with variable usage by authors, maybe add something to indicate direction to the term names themselves: "flippase (inward translocation) activity" "floppase (outward translocation) activity"

pgaudet commented 6 months ago

GO:0015248 sterol transporter activity >> have been re-annotated except for WB:WBGene00003071 and CGD:CAL0129966.

pgaudet commented 6 months ago

Dear all,

The proposal has been made to obsolete 'GO:0015248 sterol transporter activity'. The reason for obsoletion is that this term is an unnecessary grouping term; transporter activity should specific the mechanism. Please consider: GO:0034041 ABC-type sterol transporter activity, GO:0120015 sterol transfer activity and GO:0030228 - lipoprotein particle receptor activity.

There are 2 annotations to this term, see https://github.com/geneontology/go-annotation/issues/2365. There is one RHEA mapping (RHEA:39747) that will be moved as narrow match to GO:0034041 ABC-type sterol transporter activity.

You can comment on the ticket: https://github.com/geneontology/go-ontology/issues/14793

Thanks, Pascale

pgaudet commented 6 months ago

Also added RHEA xref on sterol transfer activity since RHEA also mentions NPC1L, that catalyzes intermembrane sterol transfer.

pgaudet commented 6 months ago

Changed label: GO:0005324 -name: long-chain fatty acid transporter activity +name: long-chain fatty acid transmembrane transporter activity

to match definition.

deustp01 commented 6 months ago

Reactome annotations (not listed above) have been fixed - corrected annotations will become public in June 2024 release.

pgaudet commented 6 months ago

Removed RHEA:39747 from sterol transfer activity since RHEA describes transmembrane transport and GO_0120015 intermembrane transport

deustp01 commented 6 months ago

RHEA describes transmembrane transport and GO_0120015 intermembrane transport

I tripped over this too. What is an acceptable term for sterol transmembrane transport? I didn't see one.

pgaudet commented 6 months ago

I think the ABC transporter esterifies the sterol and transports it across the membrane. Is this how you also understand the mechanism?

deustp01 commented 6 months ago

I think the ABC transporter esterifies the sterol and transports it across the membrane. Is this how you also understand the mechanism?

No. RHEA:39747 is simply cholesterol(in) = cholesterol(out), no esterification. Similarly, Reactome R-HSA-265443 "NPC1L1-mediated cholesterol uptake" is simply the movement of cholesterol with no involvement of ATP, so I don't think it fits the description of ABC transport.

deustp01 commented 6 months ago

NPC1L1 (UniProt Q9UHC9) is not an ABC transporter, so no.

pgaudet commented 6 months ago

Ha, right, this should be annotated to GO:0120015 - sterol transfer activity

deustp01 commented 6 months ago

GO:0120015 - sterol transfer activity

Or for the more specific reactions in RHEA and Reactome, its is_a child GO:0120020 cholesterol transfer activity.

I'll fix the Reactome NPC1L1 annotation accordingly for now, but I think it's still not right, because [sterol or cholesterol] transfer activity is "Removes [sterol or cholesterol] from a membrane or a monolayer lipid particle, transports it through the aqueous phase while protected in a hydrophobic pocket, and brings it to an acceptor membrane or lipid particle." while RHEA and Reactome rreactions are describing its movement across one lipid bilayer membrane, no trip through an aqueous phase to move from one lipid environment to a distant one.