MP: initiator methionine removal /GOSLIM

[gocentral]

should protein initiator methionine removal have the parent protein maturation by peptide bond cleavage?

Val

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/7131

[gocentral]

Need to be a bit careful; because Since def includes both fmet and met- N terminal protein, it might depend

1. in mammals, an enzyme with activity towards fmet-protein is found on the cell surface. It is thought that this activity is involved in removal of f-met from proteins released from bacteria, etc., However, in bacteria, the removal by the bacteirial enzyme might be considered a type of protein maturation.

Note: in eukaryotes not all initiator mets are removed (N-end rule); some are stable to this removal is not always a part of protein maturation. It depends on the protein.

Let me confer with Tom RajBhandary at MIT and I'll get back with opinion.

hjd

Original comment by: hdrabkin

[gocentral]

Ok; just talked to Tom He agrees; removal is not always part of maturation so part_of is out. As for is_a: The removal of fmet from peptides/proteins on a cell surface is a good example; not clear that it has to do with normal processing of a protein as it might be part of getting rid of bacterially derived proteins (not maturation). an is_a might be appropriate except for those cases. See for example: Enzymes degrading bacterial chemotactic F-met peptides in human ileal and colonic mucosa Journal of Gastroenterology and Hepatology Volume 5 Issue 4, Pages 375 - 381 (2008?)

Original comment by: hdrabkin

[gocentral]

So Harold,

Removal of N-met _when it occurs_during translation is always part of maturation If this is the case we need a child term to represent the eukaryotic type under maturation.

Suggestion: Removal of inititator methionine from nascent proteins parent protein maturation by peptide bond cleavage.

Would that work?

Val

Original comment by: ValWood

[gocentral]

• summary: MP: iniitator methionine removal --> MP: iniitator methionine removal /GO SLIM

Original comment by: ValWood

[gocentral]

Seems reasonable; don't know if we should restrict it to eukaryotes, since there might be cases where the f-met is removed in order to totally degrade a protein?

And during translation yes; but the removal for maturation isn't always during translation. This is a similar story for things like collagen proline hydroxylation. You can demonstrate that it occurs on native polysomes (so co-translational), but it can happen in extracts (purified proteins, etc.) so it is not clear that in vivo it always has to happen co-translationally. But when it does, it would certainly be a type of protein maturation. We need to describe a process for the removal when it is not part of maturation but perhaps degradation?

Original comment by: hdrabkin

[gocentral]

maybe we could have

protein iniitiator methionine removal --GO NEW protein inititator methionine removal involved in protein maturation

protein maturation by peptide bond cleavage --GONEW protein inititator methionine removal involved in protein maturation

?

Original comment by: ValWood

[gocentral]

Val has brought up this query again (https://sourceforge.net/tracker/?func=detail&aid=2971229&group\_id=36855&atid=440764) so I'm following it up.

Our options seem to be to either create the terms listed below by Val, or just give GO:0070084 a proteolysis parent:

proteolysis ; GO:0006508 --%protein initiator methionine removal ; GO:0070084

or both.

Harold- you know alot more about the process than me... any preferences/solutions/comments?

Thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

• assigned_to: nobody --> rfoulger

Original comment by: rebeccafoulger

[gocentral]

Getting back to this: based on the discussions below, I propose the following (basically what Val suggests):

1/ Moving 'protein initiator methionine removal ; GO:0070084' from its current parent: 'post-translational protein modification ; GO:0043687' to be a child of 'protein modification process ; GO:0006464'.

2/ Remove 'protein maturation by peptide bond cleavage ; GO:0051605' from being a child of proteolysis ; GO:0006508 because the current definition of proteolysis is the destruction of a protein.

3/ Create the new term Val suggests:

protein maturation by peptide bond cleavage ; GO:0051605 --<protein initiator methionine removal involved in protein maturation ; GO:NEW

protein initiator methionine removal ; GO:0070084 --%protein initiator methionine removal involved in protein maturation ; GO:NEW

One Q: what is the difference betwewen the following two terms?

protein processing ; GO:0016485 is_a: protein maturation ; GO:0051604 Any protein maturation process achieved by the cleavage of peptide bonds.

protein maturation by peptide bond cleavage is_a: protein processing ; GO:0016485 The hydrolysis of a peptide bond or bonds within a protein as part of protein maturation, the process leading to the attainment of the full functional capacity of a protein.

They share some (but not most) of their children. The definitions look pretty much the same to my unexpert eye.

Will check with Harold. Thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

This is just a comment on a question Becky had in her email ; To me "processing" includes any cleavages or modifications that occur to yield the "final product". Certainly in a RNA processing meeting, they would include sessions on various nucleases and base modifications, as well as turnover (degradative). I am not sure how the current def of protein processing got so restrictive " GO:0016485 Definition: Any protein maturation process achieved by the cleavage of peptide bonds.

Changing this term may be beyond the scope of this SF, but we should have Processing ....processing by cleavage ....modification

Currently, we have Maturation ... processing

Idon't see any protein modification terms under maturation. Surely if maturation is protein maturation GO id: GO:0051604 Definition: Any process leading to the attainment of the full functional capacity of a protein.

Then phosphorylation, gycosylation, etc. should be considered part of making a protein "attain it's full functional capacity".

Current children of protein maturation are only fprotein maturation [GO:0051604] ...CAAX-box protein maturation + ...patched ligand maturation ...peptide pheromone maturation + ...protein maturation by protein folding ...aprotein processing +

IF we leave protein processing cleavage only specific, then we need to consider adding children under protein maturation.

Original comment by: hdrabkin

[gocentral]

Hi Harold,

Thanks for looking at this. To answer your questions, the defs of this part of GO were revised last year: See: https://sourceforge.net/tracker/?func=detail&aid=2782290&group\_id=36855&atid=440764 and https://sourceforge.net/tracker/?func=detail&aid=1761138&group\_id=36855&atid=440764

which is when protein processing became cleavage and maturation-specific I think.

Is ALL protein modification involved in protein maturation though Harold?

I've already added a task to the wiki to relook at the modification terms (http://gocwiki.geneontology.org/index.php/Protein\_and\_peptidyl\_amino\_acid\_modification) , so I can add the processing terms to that too since I think they are broader than this SF and require some looking at in detail.

I can go ahead and do steps 1-3 for now if they look correct for this SF?

thanks! Becky

Original comment by: rebeccafoulger

[gocentral]

Yes, lets get this out the door

Original comment by: hdrabkin

[gocentral]

I set up a new SF item for my query about protein processing vs protein maturation via peptide bond cleavage: https://sourceforge.net/tracker/?func=detail&aid=3000532&group\_id=36855&atid=440764

I'll do those edits for Val's Met removal.

For your RNA processing point Harold (and the new SF item): in GO, 'RNA modification' and 'RNA processing' are siblings and we don't have any RNA modification terms under RNA processing. I've added it to the wiki that perhaps we are too restrictive in our use of 'processing'.

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

Created new term: protein initiator methionine removal involved in protein maturation ; GO:0035551

Moved protein initiator methionine removal ; GO:0070084 from post-translational protein modification ; GO:0043687' to be a child of 'protein modification process ; GO:0006464' and tweaked its definition to remove the post-translational bit

Removed 'protein maturation by peptide bond cleavage ; GO:0051605' from being a child of proteolysis ; GO:0006508 (and same for the regulation terms)

Please add any comments on protein processing vs peptide bond cleavage vs proteolysis to the new SF.

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

• status: open --> closed-accepted

Original comment by: rebeccafoulger

[gocentral]

• summary: MP: iniitator methionine removal /GO SLIM --> MP: iniitator methionine removal /GOSLIM

Original comment by: ValWood

[gocentral]

• milestone: --> PomBase

Original comment by: mah11