GO:0000155 - phosphorelay sensor kinase activity

[ValWood]

is classed as a signaling receptor activity is that correct?

[pgaudet]

Ah! I guess, in the sense that it receives a signal??

This seems incorrect @thomaspd what do you think?

[ValWood]

It's kind of weird because it isn't at the top of the pathway. Using this logic any kinase would be a receptor. It acts as a "sensor" but I don't think this should be classed as a "receptor" should it. I don't fully understand "response regulators" though. https://en.wikipedia.org/wiki/Response_regulator

[pgaudet]

Many of the sensors are TM, hence 'receptors' (I am not sure this applies to ALL, though)

[ValWood]

Ah right. I don't think ours our @Antonialock

But isn't this just 2 activities (i.e a multifunctional protein) combined into a single function term, in that case?

[pgaudet]

I ask Swiss-Prot curators for help.

[pgaudet]

Hello,

I just spoke to Catherine Rivoire at Swiss-Prot. We propose to

• [ ] Merge GO:0000155 - phosphorelay sensor kinase activity (Catalysis of the phosphorylation of a histidine residue in response to detection of an extracellular signal such as a chemical ligand or change in environment, to initiate a change in cell state or activity. The two-component sensor is a histidine kinase that autophosphorylates a histidine residue in its active site. The phosphate is then transferred to an aspartate residue in a downstream response regulator, to trigger a response.) into GO:0009927 histidine phosphotransfer kinase activity (Serves as a phospho-His intermediate enabling the transfer of phospho group between a hybrid kinase and a response regulator.) (and removing the 'signaling receptor activity' parent)

• [ ] obsolete 'GO:0000156 phosphorelay response regulator activity' (Responds to a phosphorelay sensor to initiate a change in cell state or activity. The activity of the response regulator is regulated by transfer of a phosphate from a histidine residue in the sensor, to an aspartate residue in the response regulator. Many but not all response regulators act as transcriptional regulators to elicit a response.) This does not correspond to a single activity, it just groups together proteins regulated by histidine phosphotransfer kinase. Both partners can be annotated to the process 'phosphorelay signal transduction system'.

What do you think ? Also notifying @tberardini @keseler @sandyl27 @jimhutamu

[Antonialock]

I don't think the upstream regulators of pombe mak1/2/3 (the histidine kinases) are known. I wouldn't think of them as receptors, they are not TM?

I don't understand your proposed changes Pascale I think these systems are slightly different in eukaryotes comapred to prokaryotes In prokaryotes you have "true" two-component regulatory systems, but eukaryotic systems tend to be a bit more complicated (multistep phosphorelay, not just 2 components).

in pombe we have annotated: phosphorelay sensor kinase activity - mak1, mak2, mak3, histidine phosphotransfer kinase activity - mpr1 phosphorelay response regulator activity - mcs4, prr1

e.g.

[Antonialock]

and if you obsolete GO:0000156 phosphorelay response regulator activity, then what shouldw e annotate to instead (for the cases above?)

[Antonialock]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829895/

[pgaudet]

OK very good, we will keep all the terms - in the 4-component version of the cascade, the phosphorelay sensor kinase and histidine phosphotransfer kinase activities are mediated by separate members of the pathway.

Thanks @Antonialock

[pgaudet]

I would like to hear from @thomaspd about Val's original question: is phosphorelay sensor kinase activity a signaling receptor activity? This fits the current definition of signaling receptor activity, "Receiving a signal and transmitting it in the cell to initiate a change in cell activity. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response.", but is this too vast ?

Thanks, Pascale

[tberardini]

I finally had time to look at this issue. I agree with @Antonialock. Thanks for keeping the terms.

[pgaudet]

@Antonialock I need a littte more help:

the definition is "Catalysis of the phosphorylation of a histidine residue in response to detection of an extracellular signal such as a chemical ligand or change in environment, to initiate a change in cell state or activity. The two-component sensor is a histidine kinase that autophosphorylates a histidine residue in its active site. The phosphate is then transferred to an aspartate residue in a downstream response regulator, to trigger a response."

I think that last sentence describes the GO:0009927 histidine phosphotransfer kinase activity (which is why I thought of a merge initially); do you think we should specify that this may be a different activity(in the 4-component system)?

Thanks, Pascale

[Antonialock]

Ok, this just got a bit more complicated...

Looking at wikipedia there might be a case to make these two different things in terms of MFs? (I always thought of multistep phosphorelays as a more complicated version of 2component systems, but they actually look a bit different, at least according to wikipedia...).

2 component system

1. histidine kinase (HK) autophosphorylates on a histidine residue
2. the response regulator (RR) then catalyzes the transfer of the phosphoryl group from the HK to an aspartate residue on the RR's receiver domain

multistep phosphorelay

1. HK autophosphorylates on a histidine and transfers the phosphate to an internal receiver domain
2. a histidine phosphotransferase (hPt) receives the phosphate, and transfers it to an RR. There are two types of histidine phosphotransferases: a more common monomeric without catalytic activity that interacts with one RR (it's called a "shuttle") and a less common dimeric catalytic type

assuming this is all true (it's from wikipedia....but I don't have time to dig deeper into it right now):

For 2 component systems: -HK can be annotated to GO:0000155 phosphorelay sensor kinase activity (rename term to 2-component sensor kinase activity to avoid confusion?) -Annotate RR to GO:0000156 but change the def to reflect that the RR catalyzes the transfer (note: need to check that wikipedia isn't wrong about this)

for multistep phosphorelay systems

• annotate the HK to GO:new - multistep phosphorelay sensor kinase activity, and tweak the def to reflect that the phosphate is transferred to an internal receiver domain
• annotate the hPt to GO:0009927? - may need two terms? one for dimeric catalytic proteins and one for noncatalytic monomeric proteins?
• Are these RRs orthogonal to the RRs in 2component systems? (need to check)

[pgaudet]

Hi @Antonialock

I can see a case for making two processes; but shouldn't we just make two annotations to the proteins having both sensor kinase and and phosphotrasfer activities ?

And regarding

hPt to GO:0009927? - may need two terms? one for dimeric catalytic proteins and one for noncatalytic monomeric proteins?

I suggest we use 'contributes to' for the dimeric forms; we shouldn't create separate terms.

What do you think ?

Pascale

[Antonialock]

Sounds ok I think?

I’m happy to annotate according to the excellent guidelines that accompany the terms :-P

[ValWood]

We can probably close this?

phosphorelay sensor kinase activity is no longer is_a receptor