I am looking for studies on how many protein isoforms have different functions,
ID: 31728 • Letter: I
Question
I am looking for studies on how many protein isoforms have different functions, preferably in human. We know that a great many, if not most, of human genes are alternatively spliced and that many produce different protein isoforms. Has anyone looked at how many of these isoforms have different cellular functions? If someone could point me to a published paper, that would be great.
If no such study has been made, can anyone recommend a database from which this information could be extracted? GeneOntology is gene based so the information cannot be found there. Genes will be annotated to specific terms, not their protein isoforms. Also, I would need to be able to do this in a high throughput manner, I am not interested in specific proteins but in what percentage of all isoforms have different functions.
Ideally, I would like to be able to extract, for every human gene, the list of the different protein isoforms it encodes and whether their functions differ, or at least what those functions are.
Explanation / Answer
It seems that most functional annotation these days is inferred from sequence similarity to previously annotated genes/proteins: this is certainly true of high-throughput functional annotation. It's hard to know how many layers of inference there are between your query sequence and an actual experiment verifying the (possibly tissue- or condition-specific) function of a gene/protein. But alas, I digress...
One confounding factor for is that alternatively spliced isoforms share a lot sequence in common, which means that they might share best hits when searching against a database of annotated transcripts and end up getting assigned the same GO terms.
But as others have mentioned, I think the biggest limiting factor you will encounter is the low-throughput step: in many cases the experimental work required to characterize the functions of alternative isoforms simply has not yet been done.
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