ID:NUAK1_HUMAN DESCRIPTION: RecName: Full=NUAK family SNF1-like kinase 1; EC=2.7.11.1; AltName: Full=AMPK-related protein kinase 5; Short=ARK5; AltName: Full=Omphalocele kinase 1; FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby 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 reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser- 392' and is recruited to the CDKN1A/WAF1 promoter to participate to transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Activated by phosphorylation on Thr-211. Activated by phosphorylation at Ser-600 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure. SUBUNIT: Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. INTERACTION: P04637:TP53; NbExp=5; IntAct=EBI-1046789, EBI-366083; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. TISSUE SPECIFICITY: Expressed at high levels in heart and brain, and at lower levels in skeletal muscle, kidney, ovary, placenta, lung and liver. Highly up-regulated in colorectal cancer cell lines. INDUCTION: Transcriptionally regulated by members of the MAF family. DOMAIN: The GILK motif mediates interaction with PPP1CB. PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X. PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and 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. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAA25463.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF01163 - RIO1 family PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains: 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on O60285
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0006974 cellular response to DNA damage stimulus GO:0007155 cell adhesion GO:0016310 phosphorylation GO:0030155 regulation of cell adhesion GO:0035507 regulation of myosin-light-chain-phosphatase activity GO:0035556 intracellular signal transduction GO:0042127 regulation of cell proliferation GO:1901796 regulation of signal transduction by p53 class mediator GO:2000772 regulation of cellular senescence
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
