cd05101: PTKc_FGFR2 (this model, PSSM-Id:133232 is obsolete and has been replaced by 270679)
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2
Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 2 (FGFR2); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR2 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structure of human FGFR2 tyr kinase bound to a 4-aryl-2-phenylamino pyrimidine inhibitor (1OEC_A ).