U2AF homology motif kinase 1 (UHMK1) (UHMK1)

U2AF homology motif kinase 1 (UHMK1), also known as MAPK-related kinase (MRK) or kinase interacting with stathmin (KIS), is a serine/threonine kinase that belongs to the CMGC group and the MAPK-like (MAPKL) family. It is characterized by an N-terminal kinase domain and a unique C-terminal U2AF homology motif (UHM), which enables it to regulate mRNA splicing and RNA processing by phosphorylating factors such as SF1 and SF3B1. UHMK1 is a key regulator of the cell cycle, specifically promoting the G1 to S phase transition by phosphorylating the cyclin-dependent kinase inhibitor p27 (Kip1) at Ser10, which triggers its nuclear export and subsequent degradation. In the central nervous system, UHMK1 is involved in neurite outgrowth, synaptic plasticity, and myelin formation through the phosphorylation of stathmin and myelin basic protein (MBP). Dysregulation of UHMK1 is implicated in various cancers, including colorectal, liver, and gastric cancers, where it supports tumor cell proliferation, migration, and resistance to chemotherapy. While the term "MAPK-related kinases" is sometimes used broadly to describe the JNK and p38 MAPK subfamilies or the wider MAPKL family (including NLK and MOK), UHMK1 is the primary protein specifically designated by this name in therapeutic contexts.

Other names

MAPK-related kinaseMRKKinase interacting with stathminKISKISTP-CIP2U2AF homology motif kinase 1MAPK-related kinases

Inhibition of kinase activity, modulation of p27/Kip1 nuclear export, and regulation of alternative splicing through phosphorylation of splicing factors.