NUAK family SNF1-like kinase 1; AMPK-related protein kinase 5; ARK5; omphalocele kinase 1 (NUAK1, ARK5, KIAA0537, OMPHK1)
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Function
- serine/threonine protein kinase
- role in various processes such as
- cell adhesion
- regulation of cell ploidy & cellular senescence
- cell proliferation
- tumor progression
- phosphorylates ATM, CASP6, LATS1, PPP1R12A & p53/TP53
- acts as a regulator of cellular senescence & cell ploidy by mediating phosphorylation of Ser-464 of LATS1, thus controlling its stability
- controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex
- acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1
- phosphorylated PPP1R12A then interacts with 14-3-3, leading to diminished dephosphorylation of myosin MLC2 by myosin PP1
- may be involved in DNA damage response
- may also act as a tumor malignancy-associated factor by promoting tumor invasion & metastasis under regulation & phosphorylation by AKT1
- suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thus suppressing activation of caspase & subsequent cleavage of CFLAR
- activated by phosphorylation on Thr-211
- activated by phosphorylation at Ser-600 AKT1 during glucose starvation (relevance in normal cells is unknown)
- ubiquitinated with Lys-29- & Lys-33-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation
- deubiquitinated by USP9X
- phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase & CAB39
- not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1
- phosphorylated by STK38L upon stimulation with IGF1
- interaction (via GILK motif) with PPP1CB bridges NUAK1 & PPP1R12A
Structure
- the GILK motif mediates interaction with PPP1CB
- belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, SNF1 subfamily
- contains 1 protein kinase domain
Compartment
Alternative splicing
named isoforms=2
Expression
- expressed at high levels in heart & brain
- expressed at lower levels in skeletal muscle, kidney, ovary, placenta, lung & liver
- up-regulated in colorectal cancer cell lines
- transcriptionally regulated by members of the MAF family