The SPRY domain is a protein interaction module found in 77 murine and ~100 
human proteins, and is implicated in important biological pathways, including 
those that regulate innate and adaptive immunity. The current definition of the 
SPRY domain is based on a sequence repeat discovered in the splA kinase and 
ryanodine receptors. The greater SPRY family is divided into the B30.2 (which 
contains a PRY extension at the N-terminus) and "SPRY-only" sub-families. In 
this brief review, we examine the current structural and biochemical literature 
on SPRY/B30.2 domain involvement in key immune processes and highlight a 
PRY-like 60 amino acid region in the N-terminus of "SPRY-only" proteins. 
Phylogenetic, structural, and functional analyses suggest that this N-terminal 
region is related to the PRY region of B30.2 and should be characterized as part 
of an extended SPRY domain. Greater understanding of the functional importance 
of the N-terminal region in "SPRY only" proteins will enhance our ability to 
interrogate SPRY interactions with their respective binding partners.