Molecular identifiers of the evolutionarily conserved titin pseudokinase.

ABSTRACT: Titin kinase (TK) is an enigmatic pseudokinase specific to the striated muscle of vertebrates. Embedded within the contractile sarcomere and flanked by extensible regulatory tails, TK is thought to act as a mechanoreceptor that senses mechanical signals arising from muscle function. Studies on TK so far have focused narrowly on the human representative, whose phosphotransfer activity remains questioned. To investigate whether the pseudokinase character is a hallmark of TK, we studied sequences of distantly evolved fish representatives and rationalized conservation patterns by solving the crystal structure of TK from medaka (isoform b). We find that sequence deviations in functional motifs involved in ATP and magnesium binding, respectively θxK (θ: bulky hydrophobic residue) and EFG, are ev

SUBMITTER: Dorendorf T 

PROVIDER: S-EPMC12862963 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature