cd05053: PTKc_FGFR (this model, PSSM-Id:173634 is obsolete and has been replaced by 270646)
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors
Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor (FGFR) subfamily; catalytic (c) domain. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. 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. FGFR subfamily members 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, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. 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. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human FGFR1 and FGFR2tyr kinase bound to Su5402 inhibitor inhibitor and 4-aryl-2-phenylamino pyrimidine inhibitor (1FGI_A and 1OEC_A respectively).
Jiyao W et al.(2023). "The conserved domain database in 2023.",