NTR: Toll-like receptor binding

[gocentral]

Do we need a toll-like receptor binding term in FUNCTION ?

There are 4 genes currently annotated to Toll binding ; GO:0005121: 1 Drosophila (spatzle) 1 rat 2 human (including PMID:11441107 as evidence)

Toll is the Drosophila receptor. The Toll-like receptors (TLRs) are the mammalian counterparts (there's at least 10 of them) but Toll and TLRs act in slightly different ways- the TLRs directly bind to their 'ligands' whereas Toll binds to spatzle, which binds to ligands.

We have Toll signaling, and Toll-like signaling in process. Therefore do we need a Toll-like receptor binding term in FUNCTION to transfer the mammalian annotations to?

receptor binding ; GO:0005102 --%Toll binding ; GO:0005121 --%Toll-like receptor binding ; GO:NEW

Toll-like receptor binding Interacting selectively and non-covalently with a Toll-like protein, a pattern recognition receptor that binds pattern motifs from a variety of microbial sources to initiate an innate immune response. exact synonym: TLR binding

The alternative is to broaden the definition of Toll-binding to include Toll-like receptors and add in Toll-like receptor binding and TLR binding as synonyms to the existing term.

Any comments/suggestions/objections?

The definition for Toll signaling pathway ; GO:0008063 could also do with a tweak to make it read a bit better. It currently reads as: The series of molecular signals initiated by binding of a ligand to an extracellular ligand to the Toll receptor on the surface of the target cell.

thanks, Becky

Reported by: rebeccafoulger

Original Ticket: geneontology/ontology-requests/7092

[gocentral]

Becky,

I would prefer individual terms, TLR1 binding, TLR2 binding, etc. up to TLR22 (apparently), with or without a grouping term. The TLRs vary considerably in their ligand specificity, both protein and otherwise, and I think they deserve individual terms, particularly because of the incredibly important and varying roles they play in vertebrate immune responses.

I don't know if drosophila Toll and the vertebrate TLRs should be grouped under the same term. One could argue for a Toll-superfamily binding term perhaps. Certainly I am opposed to broadening the definition of Toll binding to include TLRs, as Toll is really an insect family of proteins. We don't talk about Toll proteins in vertebrates; rather we talk about Toll-like receptors, and much more commonly just TLRs.

Thanks,

Alex

Original comment by: addiehl

[gocentral]

Added new term: Toll-like receptor binding ; GO:0035325 synonym: TLR binding

I'll add any child TLR1-22 binding terms as people request them.

Tweaked definition of Toll signaling pathway; GO:0008063.

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

• status: open --> closed-accepted

Original comment by: rebeccafoulger

[gocentral]

Becky,

I would recommend that the xrefs associated with GO:0008063 be moved to GO:0034142, as these were probably put there before GO:00341142 was available. The current term stanzas are below:

[Term] id: GO:0008063 name: Toll signaling pathway namespace: biological_process def: "The series of molecular signals initiated by binding of an extracellular ligand to the Toll receptor on the surface of the target cell." [GOC:go_curators, PMID:11135568, PMID:19126860] synonym: "Tl signaling pathway" EXACT [] synonym: "Tl signalling pathway" EXACT [] synonym: "Toll signalling pathway" EXACT [] xref: Reactome:166016 "Toll Like Receptor 4 (TLR4) Cascade" xref: Reactome:448845 "Toll Like Receptor 4 (TLR4) Cascade" xref: Reactome:469961 "Toll Like Receptor 4 (TLR4) Cascade" xref: Reactome:488101 "Toll Like Receptor 4 (TLR4) Cascade" xref: Reactome:507927 "Toll Like Receptor 4 (TLR4) Cascade" is_a: GO:0007166 ! cell surface receptor linked signaling pathway is_a: GO:0023034 ! intracellular signaling pathway

[Term] id: GO:0034142 name: toll-like receptor 4 signaling pathway namespace: biological_process def: "Any series of molecular signals generated as a consequence of binding to toll-like receptor 4." [GOC:add, PMID:16551253, PMID:17328678] synonym: "TLR4 signaling pathway" EXACT [] synonym: "toll-like receptor 4 signalling pathway" EXACT [] is_a: GO:0002224 ! toll-like receptor signaling pathway

Thanks,

Alex

Original comment by: addiehl

[gocentral]

Hi Alex,

I've transferred those 5 Reactome Xrefs over. I've contacted Amelia to see how the Reactome X-refs are generated so can fix the Reactome end too.

thanks, Becky

Original comment by: rebeccafoulger