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UBA domain found in MAP/microtubule affinity-regulating kinase MARK3, MARK4, and similar proteins MARK3, also called C-TAK1, Cdc25C-associated protein kinase 1, ELKL motif kinase 2 (EMK-2), protein kinase STK10, Ser/Thr protein kinase PAR-1 (Par-1a), or serine/threonine-protein kinase p78, is a known regulator of KSR1, a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. It binds plakophilin 2 (PKP2), phosphorylates human Cdc25C on serine 216, and promotes 14-3-3 protein binding and protein localization. It also interacts with microphthalmia-associated transcription factor, Mitf which is necessary for regulating genes involved in osteoclast differentiation. Moreover, MARK3 is involved in regulating localization and activity of class IIa histone deacetylases. The lack of MARK3 leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis. MARK4, also called MAP/microtubule affinity-regulating kinase-like 1 (MARKL1), or Par-1d, is a member of the AMP-activated protein kinase (AMPK)-related family of kinases. It plays a key role in energy metabolism and may act as a novel drug target for the treatment of obesity and type 2 diabetes. MARK4 also functions as the substrate of ubiquitin specific protease-9 (USP9X) and can be regulated by unusual Lys(29)/Lys(33)-linked polyubiquitin chains. Furthermore, MARK4 may play some role in hepatocellular carcinogenesis. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",