To better understand the evolutionary history of these proteins, we classified them into discrete families. We defined an SH2 domain family as a conserved cluster of SH2 domains that can be traced back through various lineages to a single origin and that likely represents a functionally distinct group, which may be subject to distinct evolutionary pressure. Several approaches have been used to identify relationships between different genes. All 111 human SH2 domain proteins were cataloged into 38 distinct SH2 families by means of sequence alignments, domain organization, and intron/exon splicing. For each family we determined whether an individual approach would be sufficient to categorize a family (Yes or No). If a method failed to classify a family, we noted the rea- son(s) in the comments column.