||SHB (SH2 homology protein in B/ beta -cells) is a 55-59 kDa cytoplasmic adaptor protein that serves as a link between phosphotyrosine residues and downstream signaling pathways. SHB is ubiquitously expressed, and binds tyrosine kinase receptors such as FGFR1, VEGFR2, and the TCR (zeta -chain) following their activation. It is highly modular, and through a variety of motifs, is able to bind multiple, structurally unrelated proteins that collectively generate a signal transduction network. Human SHB is 509 amino acids (aa) in length. It contains an N-terminal Pro-rich region that binds SH3 domain-containing proteins (aa 19-45， a central PTB domain that binds select aa motifs, and a C-terminal SH2 domain that interacts with phosphotyrosines (aa 410-504). There are at least nine utilized phosphorylation sites. There are two isoform variants. One is 66-68 kDa in size, and possesses an 87 aa Pro-rich N-terminal extension. This MW may increase to 77-80 kDa following posttranslational processing. A second variant shows an 18 aa substitution for aa 280-509. Over aa 2-128, human SHB shares 91% aa identity with mouse SHB.