cd05033: PTKc_EphR (this model, PSSM-Id:133165 is obsolete and has been replaced by 270629)
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases
Protein Tyrosine Kinase (PTK) family; Ephrin Receptor (EphR) subfamily; 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. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EhpB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human EphA2 receptor bound with an ATP analog and mouse EphB2 receptor tyr kinase bound with ADP, (1MQB_B, 2HEN_A respectively).
Lu S et al.(2020). "CDD/SPARCLE: the conserved domain database in 2020.",