SH2 and SH3 (Src homology) domains were originally identified as critical
functional domains within non-receptor proteins with tyrosine kinase activity.
A subset of these proteins appears to exist predominately of SH2/SH3
domains in the absence of detectable catalytic domains. One of the first
members of the family to be identified, Crk, is a transformation-specific protein
that induces elevation of cellular phosphotyrosine levels, but lacks tyrosine
kinase activity itself. A second protein, Nck, consists solely of three
SH3 domains and one SH2 domain, while GRB2 contains an SH2 domain
flanked on both sides by SH3 domains. A member of this protein class,
Crk-L, is encoded by a gene located on chromosome 22, band 11, centromeric
of the chronic myelogenous leukemia breakpoint region. Crk-L encodes
a 303 amino acid protein with one SH2 and two SH3 domains, and a predicted
molecular weight of 36 kDa.