receptor binding

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The current defintion for receptor binding seems too vague and more like a def for binding ; GO:0005488.

term: receptor binding goid: GO:0005102 definition: Interacting selectively with one or more specific sites on another molecule.

Could it be changed to something like:

Interacting selectively with one or more specific sites on a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. ref: ISBN:0 19 850673 2

Also just to check: can I annotate to 'receptor binding' and its children if the interaction is intracellular? Specifically the IRS proteins that interact with the cytoplasmic part of the insulin-/insulin-like receptor. It's quite a distinct 'function' from the 'ligand' (in the synonyms file receptor binding ~ receptor ligand) but at the moment there's no way to express this difference in the function ontology. (maybe it's sufficient to annotate to extracellular/intracellular/ in the cc part??).

Finally,

insulin-like growth factor receptor binding ; GO:0005159 is a child of transmembrane receptor protein tyrosine kinase signaling protein activity ; GO:0005066. So insulin receptor binding ; GO:0005158 probably should be too since the INR has Tyr kinase activity.

Thanks,

Becky

Reported by: beckyfoulger

Original Ticket: "geneontology/ontology-requests/934":https://sourceforge.net/p/geneontology/ontology-requests/934

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The final point - the existing relationship shouldn't be there because it describes gene product properties. I will remove it.

At the moment, 'receptor binding' is under 'signal transducer activity', which is defined as "Mediates the transfer of a signal from the outside to the inside of a cell by means other than the introduction of the signal molecule itself into the cell.". I am not sure whether this should really be a function or whether it's a process. Anyway, that def may need to be altered because I don't see why receptor binding shouldn't be intracellular, too, with the binding location specified in the cc annotation.

Original comment by: girlwithglasses

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• assigned_to: nobody --> girlwithglasses

Original comment by: girlwithglasses

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I will amend the def of 'receptor binding' to "Interacting selectively with one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function."

I would like to obsolete "signal transducer activity" because it represents a process and not a molecular function. Annotations should be redirected to the biological process term "signal transduction ; GO:0007165".

Signal transducer activity currently has several children; these could be dealt with as follows:

activin inhibitor activity ; GO:0017106 --> enzyme inhibitor activity ; GO:0004857 (?) histidine phosphotransfer kinase activity ; GO:0009927 -->kinase activity ; GO:0016301 morphogen activity ; GO:0016015 --> directly under molecular function receptor activity ; GO:0004872 --> directly under molecular function receptor binding ; GO:0005102 --> under binding ; GO:0005488 receptor signaling protein activity ; GO:0005057 --> need to work out what is actually meant by this term. It should be reworded to remove "protein" really. For the moment, can go directly under molecular function, pending a review. receptor-associated protein activity ; GO:0016962 --> this category isn't a function. The children will need to be assessed - if they are true functions, they can be rehomed, but if they look like gene products, they should be obsoleted. quorum sensing response regulator activity ; GO:0009370 quorum sensing signal generator activity ; GO:0009369 two-component response regulator activity ; GO:0000156 two-component sensor molecule activity ; GO:0000155 I think these are all gene products (I mailed the list about them a while back). Find out what functions are associated with them and then obsolete them, redirecting annotations to the appropriate functions.

Feel free to suggest alternative parents for these terms! If there are no problems, I will obsolete these terms on Aug 1st.

Original comment by: girlwithglasses

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signal transducer activity : current def

"Mediates the transfer of a signal from the outside to the inside of a cell [or cellular compartment] by means other than the introduction of the signal molecule itself into the cell."

Midori pointed out a problem in the definition: "The 'means other than the introduction of the signal molecule itself into the cell' phrase appears to exclude steroid receptors. Oops."

If we exclude the offending bit of the definition, we get

"Mediates the transfer of a signal from the outside to the inside of a cell or cellular compartment."

How is a signal transducer thus defined any different from a transporter? ("Enables the directed movement of substances (such as macromolecules, small molecules, ions) into, out of, within or between cells.").

This leads me to suggest that 'signal transducer activity' is actually a process, and annotation should be to the process term 'signal transduction ; GO:0007165' instead, and 'signal transducer activity' should be obsoleted.

Jodi Hirschman pointed out an additional true path violation: In SGD we have the yeast pheromones annotated to "pheromone activity" under "receptor binding". Seems right.
But by the true path rule, pheromones must have "signal transducer activity", meaning they:

"Mediates the transfer of a signal from the outside to the inside of a cell by means other than the introduction of the signal molecule itself into the cell."

Original comment by: girlwithglasses

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Hi Amelia,

At TAIR we only have 20 genes that are annotated to signal trasducer activity but 266 genes annotated to the children terms. So as long as the children terms are homed in the ontology we are fine. Besides, the 20 genes are all IEA annotations.

Suparna

Original comment by: smundodi

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I have a comment to the Midori's (?) comment: New def: Mediates the transfer of a signal from the outside to the inside of a cell or cellular compartment."

How is a signal transducer thus defined any different from a transporter? ("Enables the directed movement of substances (such as macromolecules, small molecules, ions) into, out of, within or between cells.").

SUbstance and signal are not the same things. A substance is always a physical entity; a signal is not. Insulin binding it's receptor is a signal, but so is heat, etc. Binding to a receptor does not mean a substance is then transported into the cell.

Original comment by: hdrabkin

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I concur that " receptor-associated protein activity" need to GO (pun!).

Many of these seem to be describing protein-protein interactions and complex formation, or even a gene product name (GO:GO:0016923, aka TRIP), and alpha-2 macroglobulin receptor-associated protein activity GO id: GO:0016963 Definition: Interaction with the alpha-2 macroglobulin receptor and glycoprotein gp330 forming a complex with the alpha-2 macroglobulin receptor light and heavy chains.

Original comment by: hdrabkin

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Hello Harold,

wrt your comment about signal transducers - is there some way we could define 'signal transducer' so that it is distinctly different from a transporter?

Original comment by: girlwithglasses

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As promised, I have been thinking about a more useable definition for signal transducing activity : I've been looking over the definitions of the individual components of "signal tranducer"; there are two components:

1. detect signal << what is this
2. change signal into another activity

signal: N. an object (an event; detectable physical quantity or impulse) used to convey information; V. to communicate

transduce: to change one energy or a message into another form (sense organs transduce physical energy (light, heat,) into chemo/ electric energy. transducer: a device that converts energy from one form into another.

A signal transducer would thus be a gene product that converts one type of signal into another.

This would distinguish it from the process of signal transduction, of which the transducer would be only one part of the whole process.

A distinction might be made between the type of signal in and out. The transducer needs to change the signal type. However, this may need to be broad: light to chemical is easy, but ligand binding to cause activation of intrinsic enzymatic activity might be harder; both are sort of chemical events although you could consider the ligand binding causing a conformational change as being chemical to physical . Note that the effect of binding is to activate the enzymatic activity. The enzymatic activity itself is separate.

Original comment by: hdrabkin

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I'm not convinced by this new definition. "Signal" still seems like a very vague concept - would every gene product involved in a signal transduction pathway be a signal transducer? If not, which proteins involved in a pathway would be called signal transducers and which wouldn't? Doesn't DNA contain a "signal" which is converted from DNA sequence to protein structure?

Even if the def is changed, we'll still have the problem that 'receptor binding' is not a true child of 'signal transducer activity', and there will still be the issue with receptors which convey the signal molecule into the cell as a means of relaying the signal.

Original comment by: girlwithglasses

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Reply to the part about transducer vs transporter: with a transporter, a substance goes in one end and out the other. the "signal" can be a substance (like a phermone), but it doesn't have to be. The transducer converts one type of signal to another ( a chemical signal (like phermone) to a conformational change , etc.

Original comment by: hdrabkin

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Hi,

While I was initially uncomfortable with the term "signal transducer" and use of the word "signal", I think we're on the road to sharpening this up. (Use of "signal"-related terms is so widespread in biology that it seems like we have to use these terms, and by doing so at least we formulate good definitions for them.)

Amelia, to answer your questions from today.. by Harold's definition:

"A signal transducer would thus be a gene product that converts one type of signal into another."

it seems possible that more than one of the proteins in a signal transduction pathway could be signal transducers, but not necessarily all of them since they all won't change the signal to another form. DNA doesn't contain a "signal" in your example, because the DNA itself is not changed in the act of making protein.

I think that Harold's definition works; a signal transducer interacts with a type of signal and converts it to a different type of signal. The result is the transmission of information.

Original comment by: jodih

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Jodi: RE: my DNA example, if DNA contains a signal, then does the translation/transcription machinery act as a signal transducer?

Harold: in the transducer vs. transporter debate - I understand the difference between transducers and transporters; however, we've got all the receptor activities lumped under 'signal transducer activity' and some receptors work by conveying the signal molecule into the cell. We can no longer therefore broadly classify all receptor activities as signal transducers - each receptor activity will need to be assessed and recategorized. Are receptors which transport a signal molecule into a cell therefore not signal transducers? Are they involved in signal transduction, though? Or would we say that there has been a change in the signal type, ie. incoming signal is extracellular steroid molecules, and the outgoing signal is intracellular steroid molecules?

Original comment by: girlwithglasses

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I don't see a transporter as a signal transducer; and a don't consider a receptor as a transporter either. If transporters are children of signal transducers, this should be changed. A transporter does not change a signal. If transporters are children of receptors, then this needs to be rethought. It's like the issue we discussed way back about whether xx transporters should be children of xx binding in all cases. Concurrent annotation would be a safer and more flexible approach.

Original comment by: hdrabkin

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Amelia,

No. First (unless I'm misunderstanding your example), DNA doesn't contain a signal for transcription to occur. DNA in and of itself is not a signal. Second, the transcription/translation machinery is carrying out a set of biosynthetic reactions that don't involve conversion of the DNA (or RNA) from one form to another. DNA and RNA, while serving as templates for the processes, aren't changed in the process. Maybe someone else can clarify this better than I can. To me there's a concrete difference between a signaling process and they type of process you're talking about, but I may not be articulating that difference well.

Original comment by: jodih

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Jodi: DNA contains information which can be converted into protein structure. Would you agree with this? Doesn't the transcription/translation machinery therefore transduce the information held in the DNA into another form, ie. a protein?

Harold: You said "I don't see a transporter as a signal transducer; and a don't consider a receptor as a transporter either.". OK, but what about receptors which transfer the signal molecule into the cell? Do we agree that you would need to annotate these proteins to both transporter and receptor activity? Would these receptors also be annotated to signal transducer activity?

I think that 'signal transducer activity' is just too broad and even with the new definition, it's easy to misinterpret and apply it to inappropriate instances - I have been trying to demonstrate this with the examples I've given. You have both said (paraphrasing) "To me, signal tranducer..." or "I see signal transducers..." - you both have a concept of what a signal transducer is, but I think that the current def and the new def fail to capture it. I think that the term 'signal transducer activity' has been used to describe the activity of anything involved in a signal transduction cascade, and by using the term thus you are not capturing any more information than you already have by annotating to the process term 'signal transduction'. If you want to have a term to represent conversion of one type of signal information into another, I think it should be a new term because I don't think that 'signal transducer activity' will have been used in this way.

Original comment by: girlwithglasses

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Signal transduction. The biochemical events that conduct the signal of a hormone or growth factor from the cell exterior, through the cell membrane, and into the cytoplasm. This involves a number of molecules, including receptors, proteins, and messengers.

Are all these proteins therefore signal transducing molecules. Certainly cytokines are accepted as signal transducing molecules with the ability to induce signal transduction via receptor binding.

I'm happy enough to remove signal transducer activity as long as can still add a function term which looks like it will always be 'blah binding..'

Ev

Original comment by: ecamon

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I'm going to close this item since we're going to discuss signal transducer at the next meeting. The other part of the query has been answered.

Original comment by: girlwithglasses

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• milestone: --> TermGenie
• status: open --> closed-postponed

Original comment by: girlwithglasses