Pseudokinase

The term "Other kinases with reduced ATP-binding" typically refers to pseudokinases, a subset of the kinome that lacks one or more of the highly conserved catalytic residues required for phosphotransferase activity. Despite being traditionally viewed as "kinase-dead," these proteins play critical roles in cellular signaling by acting as allosteric regulators, molecular scaffolds, or anchors for other signaling molecules. Pseudokinases like HER3 (ERBB3) and STRAD alpha are essential for the activation of their catalytic partners and are frequently implicated in human diseases, particularly cancer, where they can drive oncogenic signaling pathways. Therapeutic targeting of pseudokinases is an emerging field, focusing on small molecules that bind to their vestigial ATP-binding pockets to induce conformational changes or disrupt protein-protein interactions. Because they lack traditional enzymatic activity, drug development for these targets requires a deep understanding of their non-catalytic regulatory mechanisms.

Other names

Kinase-dead proteinsNon-catalytic kinasesKinase-like proteinsATP-binding deficient kinases

Inhibition of allosteric signaling or disruption of scaffolding functions through small molecule binding to the pseudo-active site.