Dual specificity protein kinase CLK3 (CLK3)

Dual specificity protein kinase CLK3 (CLK3) is a nuclear enzyme encoded by the *CLK3* gene in humans, classified as a dual specificity kinase because it phosphorylates both serine/threonine and tyrosine residues[6][9]. It belongs to the CDC-like kinase (CLK) family, with a key role in the regulation of serine/arginine-rich (SR) proteins that direct splice site selection in pre-mRNA splicing by reversible phosphorylation[2][3][7][9]. Unique structural features, including specific insertions in its kinase domain, influence substrate recognition and interaction with inhibitors[3][5]. CLK3 is implicated in alternative splicing regulation, neural development, and metabolic reprogramming, and its dysregulation — including overexpression and activating mutations — has been linked to cancer, particularly cholangiocarcinoma[2][4]. The enzyme is present primarily in the nucleus, and multiple alternatively spliced isoforms exist, one of which lacks kinase activity[6][9]. CLK3’s structural and functional uniqueness within the CLK subfamily presents challenges and opportunities for selective therapeutic targeting[2][3][5][7].

Other names

CDC-like kinase 3CDC2-like kinase 3PHCLK3/152

Inhibition of dual specificity kinase activity (serine/threonine and tyrosine kinase activity)