NUAK1

NUAK family, SNF1-like kinase, 1
Identifiers
Symbols	NUAK1 ; ARK5
External IDs	OMIM: 608130 MGI: 1925226 HomoloGene: 8896 IUPHAR: 2129 ChEMBL: 5784 GeneCards: NUAK1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • p53 binding • protein serine/threonine kinase activity • protein binding • ATP binding • metal ion binding Cellular component • nucleus • nucleolus • cytoplasm • microtubule cytoskeleton • AMP-activated protein kinase complex Biological process • protein phosphorylation • cellular response to DNA damage stimulus • cell adhesion • regulation of cell adhesion • negative regulation of TOR signaling • regulation of myosin-light-chain-phosphatase activity • intracellular signal transduction • regulation of cell proliferation • cellular response to glucose starvation • regulation of cellular senescence Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9891	77976
Ensembl	ENSG00000074590	ENSMUSG00000020032
UniProt	O60285	Q641K5
RefSeq (mRNA)	NM_014840	NM_001004363
RefSeq (protein)	NP_055655	NP_001004363
Location (UCSC)	Chr 12: 106.06 – 106.14 Mb	Chr 10: 84.37 – 84.44 Mb
PubMed search

NUAK family SNF1-like kinase 1 also known as AMPK-related protein kinase 5 (ARK5) is an enzyme that in humans is encoded by the NUAK1 gene.^[1][2][3]

Clinical significance

ARK5 is important in tumor malignancy and invasiveness.^[4]

Research findings

ARK5 is often overexpressed in multiple myeloma cell lines.^[5][6] ARK5 promotes tumor cell survival under regulation by Akt.^[4]

ARK5 increases MT1-MMP production.^[4] (MT1-MMP activates MMP-2 and MMP-9 which are involved in tumor metastasis.^[4])

As a drug target

ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.^[5]

Interactions

NUAK1 has been shown to interact with USP9X^[7] and Ubiquitin C.^[7]

References

1. Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H (Dec 2002). "Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein". J Biol Chem 278 (1): 48–53. doi:10.1074/jbc.M206025200. PMID 12409306.
2. Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Esumi H (Sep 2003). "ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation". Oncogene 22 (40): 6177–82. doi:10.1038/sj.onc.1206899. PMID 13679856.
3. "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1".
4. Suzuki A, Lu J, Kusakai G et al. (2004). "ARK5 is a tumor invasion-associated factor downstream of Akt signaling.". Mol. Cell. Biol. 24 (8): 3526–35. doi:10.1128/MCB.24.8.3526-3535.2004. PMC 381626. PMID 15060171.
5. Multi-Target Drug Blocks Myeloma Proliferation. March 2016
6. Deepak Perumal et al. "Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 is effective in vitro and in vivo in Multiple Myeloma.". Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1324. doi:10.1158/1538-7445.AM2014-1324.
7. Al-Hakim, Abdallah K; Zagorska Anna; Chapman Louise; Deak Maria; Peggie Mark; Alessi Dario R (Apr 2008). "Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains". Biochem. J. (England) 411 (2): 249–60. doi:10.1042/BJ20080067. PMID 18254724.

Further reading

• Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.". DNA Res. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Lizcano JM, Göransson O, Toth R, et al. (2005). "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.". EMBO J. 23 (4): 833–43. doi:10.1038/sj.emboj.7600110. PMC 381014. PMID 14976552.
• Suzuki A, Kusakai G, Kishimoto A, et al. (2004). "Regulation of caspase-6 and FLIP by the AMPK family member ARK5.". Oncogene 23 (42): 7067–75. doi:10.1038/sj.onc.1207963. PMID 15273717.
• Kusakai G, Suzuki A, Ogura T, et al. (2005). "Strong association of ARK5 with tumor invasion and metastasis.". J. Exp. Clin. Cancer Res. 23 (2): 263–8. PMID 15354411.
• Suzuki A, Iida S, Kato-Uranishi M, et al. (2006). "ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma.". Oncogene 24 (46): 6936–44. doi:10.1038/sj.onc.1208844. PMID 16044163.
• Al-Hakim AK, Göransson O, Deak M, et al. (2006). "14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK.". J. Cell. Sci. 118 (Pt 23): 5661–73. doi:10.1242/jcs.02670. PMID 16306228.
• Suzuki A, Ogura T, Esumi H (2006). "NDR2 acts as the upstream kinase of ARK5 during insulin-like growth factor-1 signaling.". J. Biol. Chem. 281 (20): 13915–21. doi:10.1074/jbc.M511354200. PMID 16488889.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.