Pseudokinase

Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological and pathophysiological functions.

History

The phrase pseudokinase was first coined in 2002. They were subsequently sub-classified into different 'classes'. Several pseudokinase-containing families are found in the human kinome, including the Tribbles pseudokinases, which are at the interface between kinase and ubiquitin E3 ligase signalling.
The human pseudokinases. Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase and non ePK-related pseudoenzyme proteins. Some pseudokinases can still bind to ATP, or catalyse an atypical reaction involving migrated catalytic residues; moreover structural prediction algorithms such as AlphaFold can be used to analyse pseudokinase folding Some pseudokinases show species specific adaptions, including the vertebrate pseudokinase PSKH2, which like the closely related secretory-pathway Ser/Thr kinase PSKH1 is a client of the HSP90 molecular chaperone system in human cells.