 Several other tyrosine kinases, including epidermal growth factor receptor, insulin-like growth factor 1 receptor, colony stimulating factor 1 receptor, c-Src, Janus kinase 2, TYK2, and focal adhesion kinase as well as other tyrosine-phosphorylated proteins, including BCAR1, DOK1, beta-catenin and cortactin have also been described as PTP1B substrates.The first crystal structure of the PTP1B catalytic domain revealed that the catalytic site exists within a deep cleft of the protein formed by three loops including the WPD loop with the Asp181 residue, a pTyr loop with the Tyr46 residue and a Q loop with the Gln262 residue.The pTyr loop and Tyr46 residue are located on the surface of the protein, and thus help to determine the depth a substrate can obtain within the cleft.