U2AF homology motif kinase 1 (UHMK1)

U2AF homology motif kinase 1 (UHMK1) is a unique serine/threonine protein kinase notable for possessing the U2AF homology motif (UHM), typically found in RNA-binding and spliceosomal proteins. UHMK1 regulates key steps in alternative and canonical mRNA splicing by phosphorylating splicing factors such as SF1 and SF3B1. Additionally, it controls cell cycle progression by targeting CDKN1B/p27Kip1 for phosphorylation, influencing cell division and proliferation. UHMK1 is abnormally upregulated in several cancers, contributing to tumor progression and chemoresistance (notably via interaction with STAT3 and PI3K/AKT/mTOR pathways). It is also associated with neurological conditions such as schizophrenia. UHMK1 is actively studied for its role in gene regulation, cell migration, and as a potential therapeutic target in oncology. No selective clinical UHMK1 inhibitors are established as of now.

Other names

Serine/threonine-protein kinase KistUHMK1KISKISTP-CIP2Kinase interacting with stathminPAM COOH-terminal interactor protein 2Kinase interacting with leukemia-associated gene (stathmin)

Inhibition of UHMK1 kinase activity would block phosphorylation of cell cycle and splicing proteins, potentially reducing cell proliferation and reversing chemoresistance. Targeting UHMK1 can modulate PI3K/AKT/mTOR and IL6/STAT3 signaling pathways, impacting cancer progression