Human protein kinases (Kinome)

The human kinome comprises a large family of approximately 518 enzymes that regulate biological processes by catalyzing the phosphorylation of proteins. By transferring a gamma-phosphate group from ATP to serine, threonine, or tyrosine residues, these kinases act as molecular switches that control signal transduction pathways, cell cycle progression, and metabolic activities (Manning et al., 2002, Science). Aberrant kinase signaling, often resulting from genetic mutations or overexpression, is a hallmark of numerous pathologies, including various cancers, rheumatoid arthritis, and cardiovascular disorders (Roskoski, 2023, Pharmacological Research). Because of their central role in disease, kinases have become one of the most intensively studied classes of drug targets, leading to the development of over 70 FDA-approved small-molecule inhibitors (Attwood et al., 2021, Nature Reviews Drug Discovery). These drugs typically function by competing with ATP for the binding site or by inducing conformational changes that lock the enzyme in an inactive state. Despite their therapeutic success, challenges such as the development of acquired resistance and the need for high selectivity to minimize off-target toxicities remain significant hurdles in kinase-targeted therapy (Bhullar et al., 2018, Molecular Cancer).

Other names

KinomeProtein phosphotransferasesProtein tyrosine kinasesSerine/threonine kinasesDual-specificity kinases

ATP-competitive inhibition, allosteric inhibition, covalent (irreversible) inhibition, and Type I-IV kinase inhibition (Roskoski, 2023, Pharmacological Research).