About SH3 Domain:
Containing about 60 amino acid residues, the SRC Homology 3 Domain is a small protein domain. While SH3 domain is typically found in tyrosine kinases, it has also been associated with and identified in multiple other protein families. Some of the more notable of these are Ras GTPase-activating protein and PI3 Kinase.
While SH3 is known for its binding effect, it typically does this away from the active site. There are about 300 of these domains seen within the human genome.
SH3 Domain Structure
SH3 domains are made up of a beta-barrel fold, which has become quite characteristic of it. There are also five or six β-strands, which are typically tightly packed and arranged as anti-parallel β sheets. Short helices can also be found in the linker regions.
SH3 Domain Interactomes
How SH3 domains interact depend on where it’s found, with this being significantly different between certain areas and genomes. There can also be many similarities, some of which can be surprising.
An SH3 interactome in a worm, for instance, can resemble how the same process in yeast. Despite this, interactions can be highly rewired between the two, especially in orthologous interactomes.
SH3 Domain Binding Specificity
SH3 domain behaves somewhat differently than some similar proteins. One of the more notable differences is that it binds far from the active site. There are some other differences, however. While the proteins are typically restricted to intracellular proteins in humans, they can also be found in the MIA family among small humans.
These will typically have an SH3-like fold, although this will be relatively small. Regardless of its location, the binding process will be the same. Usually, this will be done with the target binding partner’s proline-rich peptides.