Orphan receptor are those receptors which don't have their endogenous ligands in the body. But still these are present in our body. What is their physiological role in our body?
i was under the impression that it more means that orphan receptors dont have a indentified ligand yet. That means that they are functional, and sometimes we know exactly what they do, but we dont know what triggers them.
For one thing, at least part of the explanation probably lies in semantics - it's not necessarily that they don't have an endogenous ligand, it's that none have been discovered so far.
a related question then - what (if any) is the best resource/database to search for already discovered functions of receptors (not ligands, as these might be already known, at least partially)?
In particular what is the native role of the glycan endothelial receptors, so conveniently used by e.g. flu virus hemagglutinin as the I-st step of the virion fusion?
@Jan, i would think your best bet is to use Pathway analysis tools (i.e KEGG). Micro-array analysis often make use of pathway analysis to make the abundance of information on expression more understandable. These software packages indicate which proteins are coupled/correlated with each other, you might be able to use them to understand the normal biology of these receptor functions and from there deliniated why the virus particulary uses these receptors for their interaction.
@Jeroen, thanks - however, this seems to assume a prior access to such microarray or other experimental data; I was thinking rather in terms of searching some public database repositories in a [semi]automated manner - if/when it might be viable (and the data accessible)
@Jan, you can browse pathways within KEGG. If you were to find pathways were glycan binding receptors are involved this might be a good startpoint: http://www.genome.jp/kegg/pathway.html (choose 1.7; glycan binding proteins)
In many cases, orphan receptors have been identified by homology, so there is a presumption that they have ligand binding pockets. But some such as HER2 and the NR4As are constitutively active, whereas some have been shown to act primary as dimerization partners for other receptors (this could be stated for the examples described above). Then as stated above, some ligands haven't been found yet, and orphans are "waiting to be adopted".
@Jeroen, indeed, a good starting point, although now I'm lost in a forest of very many different types of [mostly] lectins - seems quite a bit away from my [still pretty limited] expertise in flu viral hemagglutinin binding to those sialic receptors - many thanks for your tips :)
@Chris are the homology modeling principles behind the operation of the search engine of e.g. KEGG Jeroen linked in his answer?
I've asked yet another related question separately, but either the answer is glaringly obvious (and hence my question very naive), or... no one knows yet, hard to tell for an outsider from the field: https://www.researchgate.net/post/The_role_of_lectins_in_cellular_pathways :)
To my understanding, the KEGG database looks more at the linkage of specific pathways suggested by co-expression etc, but won't necassarily correlate to physiological functions. I would use a database like Genecards.org. I f remember correctly, this site will give you the most typically agreed upon function for a particular gene with links to other informatics resources. You could also look for the knock-out or overexpression phenotype at mouse genome informatics informatics.jax.org. Each source should be referenced well enough so you can find the primary literature.
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