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Pseudokinase domain of Ryk (Receptor related to tyrosine kinase) Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",