Structure and Specificity
Some GEFs are specific to a single GTPase while others have multiple GTPase substrates. While different subfamilies of Ras superfamily GTPases have a conserved GTP binding domain, this is not the case for GEFs. Different families of GEFs correspond to different Ras subfamilies. The functional domains of these GEF families are not structurally related and do not share sequence homology. These GEF domains appear to be evolutionarily unrelated despite similar function and substrates.
Read more about this topic: Guanine Nucleotide Exchange Factor
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