Full text data of NUAK1
NUAK1
(ARK5, KIAA0537, OMPHK1)
[Confidence: low (only semi-automatic identification from reviews)]
NUAK family SNF1-like kinase 1; 2.7.11.1 (AMPK-related protein kinase 5; ARK5; Omphalocele kinase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
NUAK family SNF1-like kinase 1; 2.7.11.1 (AMPK-related protein kinase 5; ARK5; Omphalocele kinase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O60285
ID NUAK1_HUMAN Reviewed; 661 AA.
AC O60285; A7MD39; Q96KA8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=NUAK family SNF1-like kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=AMPK-related protein kinase 5;
DE Short=ARK5;
DE AltName: Full=Omphalocele kinase 1;
GN Name=NUAK1; Synonyms=ARK5, KIAA0537, OMPHK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION,
RP PHOSPHORYLATION AT THR-211, AND MUTAGENESIS OF THR-211.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A.,
RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,
RA Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK
RT subfamily, including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH AKT1, PHOSPHORYLATION AT SER-600 BY AKT1,
RP AND MUTAGENESIS OF SER-600.
RX PubMed=12409306; DOI=10.1074/jbc.M206025200;
RA Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F.,
RA Esumi H.;
RT "Identification of a novel protein kinase mediating Akt survival
RT signaling to the ATM protein.";
RL J. Biol. Chem. 278:48-53(2003).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14982852;
RA Kusakai G., Suzuki A., Ogura T., Miyamoto S., Ochiai A., Kaminishi M.,
RA Esumi H.;
RT "ARK5 expression in colorectal cancer and its implications for tumor
RT progression.";
RL Am. J. Pathol. 164:987-995(2004).
RN [9]
RP FUNCTION.
RX PubMed=15060171; DOI=10.1128/MCB.24.8.3526-3535.2004;
RA Suzuki A., Lu J., Kusakai G., Kishimoto A., Ogura T., Esumi H.;
RT "ARK5 is a tumor invasion-associated factor downstream of Akt
RT signaling.";
RL Mol. Cell. Biol. 24:3526-3535(2004).
RN [10]
RP FUNCTION.
RX PubMed=15273717; DOI=10.1038/sj.onc.1207963;
RA Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S.,
RA Ogura T., Ochiai A., Esumi H.;
RT "Regulation of caspase-6 and FLIP by the AMPK family member ARK5.";
RL Oncogene 23:7067-7075(2004).
RN [11]
RP INDUCTION.
RX PubMed=16044163; DOI=10.1038/sj.onc.1208844;
RA Suzuki A., Iida S., Kato-Uranishi M., Tajima E., Zhan F., Hanamura I.,
RA Huang Y., Ogura T., Takahashi S., Ueda R., Barlogie B.,
RA Shaughnessy J. Jr., Esumi H.;
RT "ARK5 is transcriptionally regulated by the Large-MAF family and
RT mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a
RT new molecular determinant of malignant multiple myeloma.";
RL Oncogene 24:6936-6944(2005).
RN [12]
RP INDUCTION.
RX PubMed=16424013; DOI=10.1158/0008-5472.CAN-05-2154;
RA Morito N., Yoh K., Fujioka Y., Nakano T., Shimohata H., Hashimoto Y.,
RA Yamada A., Maeda A., Matsuno F., Hata H., Suzuki A., Imagawa S.,
RA Mitsuya H., Esumi H., Koyama A., Yamamoto M., Mori N., Takahashi S.;
RT "Overexpression of c-Maf contributes to T-cell lymphoma in both mice
RT and human.";
RL Cancer Res. 66:812-819(2006).
RN [13]
RP PHOSPHORYLATION BY STK38L.
RX PubMed=16488889; DOI=10.1074/jbc.M511354200;
RA Suzuki A., Ogura T., Esumi H.;
RT "NDR2 acts as the upstream kinase of ARK5 during insulin-like growth
RT factor-1 signaling.";
RL J. Biol. Chem. 281:13915-13921(2006).
RN [14]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP9X.
RX PubMed=18254724; DOI=10.1042/BJ20080067;
RA Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M.,
RA Alessi D.R.;
RT "Control of AMPK-related kinases by USP9X and atypical
RT Lys(29)/Lys(33)-linked polyubiquitin chains.";
RL Biochem. J. 411:249-260(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-22; THR-211 AND SER-455, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF LYS-84; THR-211 AND SER-600.
RX PubMed=19927127; DOI=10.1038/emboj.2009.342;
RA Humbert N., Navaratnam N., Augert A., Da Costa M., Martien S.,
RA Wang J., Martinez D., Abbadie C., Carling D., de Launoit Y., Gil J.,
RA Bernard D.;
RT "Regulation of ploidy and senescence by the AMPK-related kinase
RT NUAK1.";
RL EMBO J. 29:376-386(2010).
RN [17]
RP FUNCTION, INTERACTION WITH PPP1CB, DOMAIN GILK, MUTAGENESIS OF
RP 400-ILE-LEU-401, AND PHOSPHORYLATION AT THR-211.
RX PubMed=20354225; DOI=10.1126/scisignal.2000616;
RA Zagorska A., Deak M., Campbell D.G., Banerjee S., Hirano M.,
RA Aizawa S., Prescott A.R., Alessi D.R.;
RT "New roles for the LKB1-NUAK pathway in controlling myosin phosphatase
RT complexes and cell adhesion.";
RL Sci. Signal. 3:RA25-RA25(2010).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-84 AND THR-211.
RX PubMed=21317932; DOI=10.1038/onc.2011.19;
RA Hou X., Liu J.E., Liu W., Liu C.Y., Liu Z.Y., Sun Z.Y.;
RT "A new role of NUAK1: directly phosphorylating p53 and regulating cell
RT proliferation.";
RL Oncogene 30:2933-2942(2011).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-419 AND ARG-543.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various
CC processes such as cell adhesion, regulation of cell ploidy and
CC senescence, cell proliferation and tumor progression.
CC Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a
CC regulator of cellular senescence and cellular ploidy by mediating
CC phosphorylation of 'Ser-464' of LATS1, thereby controlling its
CC stability. Controls cell adhesion by regulating activity of the
CC myosin protein phosphatase 1 (PP1) complex. Acts by mediating
CC phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated
CC PPP1R12A then interacts with 14-3-3, leading to reduced
CC dephosphorylation of myosin MLC2 by myosin PP1. May be involved in
CC DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-
CC 392' and is recruited to the CDKN1A/WAF1 promoter to participate
CC to transcription activation by p53/TP53. May also act as a tumor
CC malignancy-associated factor by promoting tumor invasion and
CC metastasis under regulation and phosphorylation by AKT1.
CC Suppresses Fas-induced apoptosis by mediating phosphorylation of
CC CASP6, thereby suppressing the activation of the caspase and the
CC subsequent cleavage of CFLAR.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-211.
CC Activated by phosphorylation at Ser-600 AKT1 during glucose
CC starvation; the relevance of such activation in normal cells is
CC however unsure.
CC -!- SUBUNIT: Interact (via GILK motif) with PPP1CB; the interaction is
CC direct and bridges NUAK1 and PPP1R12A.
CC -!- INTERACTION:
CC O95835:LATS1; NbExp=2; IntAct=EBI-1046789, EBI-444209;
CC P04637:TP53; NbExp=5; IntAct=EBI-1046789, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60285-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60285-2; Sequence=VSP_014236, VSP_014237;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart and brain,
CC and at lower levels in skeletal muscle, kidney, ovary, placenta,
CC lung and liver. Highly up-regulated in colorectal cancer cell
CC lines.
CC -!- INDUCTION: Transcriptionally regulated by members of the MAF
CC family.
CC -!- DOMAIN: The GILK motif mediates interaction with PPP1CB.
CC -!- PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked
CC polyubiquitins which appear to impede LKB1-mediated
CC phosphorylation. Deubiquitinated by USP9X.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with
CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not
CC dephosphorylated by the myosin PP1 complex when regulating its
CC activity, due to the presence of PPP1R12A, which prevents myosin
CC PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon
CC stimulation with IGF1.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. SNF1 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25463.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AB011109; BAA25463.2; ALT_INIT; mRNA.
DR EMBL; AK027302; BAB55026.1; -; mRNA.
DR EMBL; AK289992; BAF82681.1; -; mRNA.
DR EMBL; AC010182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97768.1; -; Genomic_DNA.
DR EMBL; BC152462; AAI52463.1; -; mRNA.
DR RefSeq; NP_055655.1; NM_014840.2.
DR UniGene; Hs.524692; -.
DR ProteinModelPortal; O60285; -.
DR SMR; O60285; 19-341.
DR IntAct; O60285; 4.
DR MINT; MINT-6772082; -.
DR STRING; 9606.ENSP00000261402; -.
DR BindingDB; O60285; -.
DR ChEMBL; CHEMBL5784; -.
DR GuidetoPHARMACOLOGY; 2129; -.
DR PhosphoSite; O60285; -.
DR PaxDb; O60285; -.
DR PRIDE; O60285; -.
DR DNASU; 9891; -.
DR Ensembl; ENST00000261402; ENSP00000261402; ENSG00000074590.
DR GeneID; 9891; -.
DR KEGG; hsa:9891; -.
DR UCSC; uc001tlj.1; human.
DR CTD; 9891; -.
DR GeneCards; GC12M106457; -.
DR HGNC; HGNC:14311; NUAK1.
DR HPA; HPA027455; -.
DR MIM; 608130; gene.
DR neXtProt; NX_O60285; -.
DR PharmGKB; PA142671242; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000004864; -.
DR HOVERGEN; HBG007160; -.
DR InParanoid; O60285; -.
DR KO; K08800; -.
DR OMA; NRPRPQY; -.
DR OrthoDB; EOG7MD4PN; -.
DR PhylomeDB; O60285; -.
DR SignaLink; O60285; -.
DR ChiTaRS; NUAK1; human.
DR GeneWiki; NUAK1; -.
DR GenomeRNAi; 9891; -.
DR NextBio; 37291; -.
DR PRO; PR:O60285; -.
DR ArrayExpress; O60285; -.
DR Bgee; O60285; -.
DR CleanEx; HS_NUAK1; -.
DR Genevestigator; O60285; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
DR GO; GO:2000772; P:regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0035507; P:regulation of myosin-light-chain-phosphatase activity; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Cell adhesion;
KW Complete proteome; Cytoplasm; DNA damage; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1 661 NUAK family SNF1-like kinase 1.
FT /FTId=PRO_0000086453.
FT DOMAIN 55 306 Protein kinase.
FT NP_BIND 61 69 ATP (By similarity).
FT MOTIF 399 402 GILK motif.
FT ACT_SITE 178 178 Proton acceptor (By similarity).
FT BINDING 84 84 ATP (Probable).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 22 22 Phosphoserine.
FT MOD_RES 211 211 Phosphothreonine; by LKB1.
FT MOD_RES 455 455 Phosphoserine.
FT MOD_RES 600 600 Phosphoserine; by PKB/AKT1.
FT VAR_SEQ 182 208 ENILLDDNCNIKIADFGLSNLYQKDKF -> KKTSRENQVT
FT TLPQSAVSLRSCWTVMM (in isoform 2).
FT /FTId=VSP_014236.
FT VAR_SEQ 209 661 Missing (in isoform 2).
FT /FTId=VSP_014237.
FT VARIANT 419 419 G -> D (in dbSNP:rs55774704).
FT /FTId=VAR_040963.
FT VARIANT 543 543 P -> R (in dbSNP:rs3741883).
FT /FTId=VAR_017246.
FT MUTAGEN 84 84 K->A: Abolishes kinase activity and
FT ability to induce senescence.
FT MUTAGEN 211 211 T->A: Prevents phosphorylation and
FT activation by STK11/LKB1 complex.
FT Abolishes ability to induce senescence.
FT MUTAGEN 400 401 IL->KK: Abolishes interaction with PPP1CB
FT and ability to regulate myosin PP1
FT activity.
FT MUTAGEN 600 600 S->A: Abrogates phosphorylation by
FT PKB/AKT1. Does not affect ability to
FT induce senescence.
FT CONFLICT 86 86 I -> V (in Ref. 3; BAB55026).
SQ SEQUENCE 661 AA; 74305 MW; 806F37D52CA4718F CRC64;
MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN LKHRYELQET
LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI RREIEIMSSL NHPHIISIYE
VFENKDKIVI IMEYASKGEL YDYISERRRL SERETRHFFR QIVSAVHYCH KNGVVHRDLK
LENILLDDNC NIKIADFGLS NLYQKDKFLQ TFCGSPLYAS PEIVNGRPYR GPEVDSWALG
VLLYTLVYGT MPFDGFDHKN LIRQISSGEY REPTQPSDAR GLIRWMLMVN PDRRATIEDI
ANHWWVNWGY KSSVCDCDAL HDSESPLLAR IIDWHHRSTG LQADTEAKMK GLAKPTTSEV
MLERQRSLKK SKKENDFAQS GQDAVPESPS KLSSKRPKGI LKKRSNSEHR SHSTGFIEGV
VGPALPSTFK MEQDLCRTGV LLPSSPEAEV PGKLSPKQSA TMPKKGILKK TQQRESGYYS
SPERSESSEL LDSNDVMGSS IPSPSPPDPA RVTSHSLSCR RKGILKHSSK YSAGTMDPAL
VSPEMPTLES LSEPGVPAEG LSRSYSRPSS VISDDSVLSS DSFDLLDLQE NRPARQRIRS
CVSAENFLQI QDFEGLQNRP RPQYLKRYRN RLADSSFSLL TDMDDVTQVY KQALEICSKL
N
//
ID NUAK1_HUMAN Reviewed; 661 AA.
AC O60285; A7MD39; Q96KA8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=NUAK family SNF1-like kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=AMPK-related protein kinase 5;
DE Short=ARK5;
DE AltName: Full=Omphalocele kinase 1;
GN Name=NUAK1; Synonyms=ARK5, KIAA0537, OMPHK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION,
RP PHOSPHORYLATION AT THR-211, AND MUTAGENESIS OF THR-211.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A.,
RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,
RA Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK
RT subfamily, including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH AKT1, PHOSPHORYLATION AT SER-600 BY AKT1,
RP AND MUTAGENESIS OF SER-600.
RX PubMed=12409306; DOI=10.1074/jbc.M206025200;
RA Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F.,
RA Esumi H.;
RT "Identification of a novel protein kinase mediating Akt survival
RT signaling to the ATM protein.";
RL J. Biol. Chem. 278:48-53(2003).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14982852;
RA Kusakai G., Suzuki A., Ogura T., Miyamoto S., Ochiai A., Kaminishi M.,
RA Esumi H.;
RT "ARK5 expression in colorectal cancer and its implications for tumor
RT progression.";
RL Am. J. Pathol. 164:987-995(2004).
RN [9]
RP FUNCTION.
RX PubMed=15060171; DOI=10.1128/MCB.24.8.3526-3535.2004;
RA Suzuki A., Lu J., Kusakai G., Kishimoto A., Ogura T., Esumi H.;
RT "ARK5 is a tumor invasion-associated factor downstream of Akt
RT signaling.";
RL Mol. Cell. Biol. 24:3526-3535(2004).
RN [10]
RP FUNCTION.
RX PubMed=15273717; DOI=10.1038/sj.onc.1207963;
RA Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S.,
RA Ogura T., Ochiai A., Esumi H.;
RT "Regulation of caspase-6 and FLIP by the AMPK family member ARK5.";
RL Oncogene 23:7067-7075(2004).
RN [11]
RP INDUCTION.
RX PubMed=16044163; DOI=10.1038/sj.onc.1208844;
RA Suzuki A., Iida S., Kato-Uranishi M., Tajima E., Zhan F., Hanamura I.,
RA Huang Y., Ogura T., Takahashi S., Ueda R., Barlogie B.,
RA Shaughnessy J. Jr., Esumi H.;
RT "ARK5 is transcriptionally regulated by the Large-MAF family and
RT mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a
RT new molecular determinant of malignant multiple myeloma.";
RL Oncogene 24:6936-6944(2005).
RN [12]
RP INDUCTION.
RX PubMed=16424013; DOI=10.1158/0008-5472.CAN-05-2154;
RA Morito N., Yoh K., Fujioka Y., Nakano T., Shimohata H., Hashimoto Y.,
RA Yamada A., Maeda A., Matsuno F., Hata H., Suzuki A., Imagawa S.,
RA Mitsuya H., Esumi H., Koyama A., Yamamoto M., Mori N., Takahashi S.;
RT "Overexpression of c-Maf contributes to T-cell lymphoma in both mice
RT and human.";
RL Cancer Res. 66:812-819(2006).
RN [13]
RP PHOSPHORYLATION BY STK38L.
RX PubMed=16488889; DOI=10.1074/jbc.M511354200;
RA Suzuki A., Ogura T., Esumi H.;
RT "NDR2 acts as the upstream kinase of ARK5 during insulin-like growth
RT factor-1 signaling.";
RL J. Biol. Chem. 281:13915-13921(2006).
RN [14]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP9X.
RX PubMed=18254724; DOI=10.1042/BJ20080067;
RA Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M.,
RA Alessi D.R.;
RT "Control of AMPK-related kinases by USP9X and atypical
RT Lys(29)/Lys(33)-linked polyubiquitin chains.";
RL Biochem. J. 411:249-260(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-22; THR-211 AND SER-455, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF LYS-84; THR-211 AND SER-600.
RX PubMed=19927127; DOI=10.1038/emboj.2009.342;
RA Humbert N., Navaratnam N., Augert A., Da Costa M., Martien S.,
RA Wang J., Martinez D., Abbadie C., Carling D., de Launoit Y., Gil J.,
RA Bernard D.;
RT "Regulation of ploidy and senescence by the AMPK-related kinase
RT NUAK1.";
RL EMBO J. 29:376-386(2010).
RN [17]
RP FUNCTION, INTERACTION WITH PPP1CB, DOMAIN GILK, MUTAGENESIS OF
RP 400-ILE-LEU-401, AND PHOSPHORYLATION AT THR-211.
RX PubMed=20354225; DOI=10.1126/scisignal.2000616;
RA Zagorska A., Deak M., Campbell D.G., Banerjee S., Hirano M.,
RA Aizawa S., Prescott A.R., Alessi D.R.;
RT "New roles for the LKB1-NUAK pathway in controlling myosin phosphatase
RT complexes and cell adhesion.";
RL Sci. Signal. 3:RA25-RA25(2010).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-84 AND THR-211.
RX PubMed=21317932; DOI=10.1038/onc.2011.19;
RA Hou X., Liu J.E., Liu W., Liu C.Y., Liu Z.Y., Sun Z.Y.;
RT "A new role of NUAK1: directly phosphorylating p53 and regulating cell
RT proliferation.";
RL Oncogene 30:2933-2942(2011).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-419 AND ARG-543.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various
CC processes such as cell adhesion, regulation of cell ploidy and
CC senescence, cell proliferation and tumor progression.
CC Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a
CC regulator of cellular senescence and cellular ploidy by mediating
CC phosphorylation of 'Ser-464' of LATS1, thereby controlling its
CC stability. Controls cell adhesion by regulating activity of the
CC myosin protein phosphatase 1 (PP1) complex. Acts by mediating
CC phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated
CC PPP1R12A then interacts with 14-3-3, leading to reduced
CC dephosphorylation of myosin MLC2 by myosin PP1. May be involved in
CC DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-
CC 392' and is recruited to the CDKN1A/WAF1 promoter to participate
CC to transcription activation by p53/TP53. May also act as a tumor
CC malignancy-associated factor by promoting tumor invasion and
CC metastasis under regulation and phosphorylation by AKT1.
CC Suppresses Fas-induced apoptosis by mediating phosphorylation of
CC CASP6, thereby suppressing the activation of the caspase and the
CC subsequent cleavage of CFLAR.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-211.
CC Activated by phosphorylation at Ser-600 AKT1 during glucose
CC starvation; the relevance of such activation in normal cells is
CC however unsure.
CC -!- SUBUNIT: Interact (via GILK motif) with PPP1CB; the interaction is
CC direct and bridges NUAK1 and PPP1R12A.
CC -!- INTERACTION:
CC O95835:LATS1; NbExp=2; IntAct=EBI-1046789, EBI-444209;
CC P04637:TP53; NbExp=5; IntAct=EBI-1046789, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60285-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60285-2; Sequence=VSP_014236, VSP_014237;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart and brain,
CC and at lower levels in skeletal muscle, kidney, ovary, placenta,
CC lung and liver. Highly up-regulated in colorectal cancer cell
CC lines.
CC -!- INDUCTION: Transcriptionally regulated by members of the MAF
CC family.
CC -!- DOMAIN: The GILK motif mediates interaction with PPP1CB.
CC -!- PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked
CC polyubiquitins which appear to impede LKB1-mediated
CC phosphorylation. Deubiquitinated by USP9X.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with
CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not
CC dephosphorylated by the myosin PP1 complex when regulating its
CC activity, due to the presence of PPP1R12A, which prevents myosin
CC PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon
CC stimulation with IGF1.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. SNF1 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25463.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
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DR EMBL; AB011109; BAA25463.2; ALT_INIT; mRNA.
DR EMBL; AK027302; BAB55026.1; -; mRNA.
DR EMBL; AK289992; BAF82681.1; -; mRNA.
DR EMBL; AC010182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97768.1; -; Genomic_DNA.
DR EMBL; BC152462; AAI52463.1; -; mRNA.
DR RefSeq; NP_055655.1; NM_014840.2.
DR UniGene; Hs.524692; -.
DR ProteinModelPortal; O60285; -.
DR SMR; O60285; 19-341.
DR IntAct; O60285; 4.
DR MINT; MINT-6772082; -.
DR STRING; 9606.ENSP00000261402; -.
DR BindingDB; O60285; -.
DR ChEMBL; CHEMBL5784; -.
DR GuidetoPHARMACOLOGY; 2129; -.
DR PhosphoSite; O60285; -.
DR PaxDb; O60285; -.
DR PRIDE; O60285; -.
DR DNASU; 9891; -.
DR Ensembl; ENST00000261402; ENSP00000261402; ENSG00000074590.
DR GeneID; 9891; -.
DR KEGG; hsa:9891; -.
DR UCSC; uc001tlj.1; human.
DR CTD; 9891; -.
DR GeneCards; GC12M106457; -.
DR HGNC; HGNC:14311; NUAK1.
DR HPA; HPA027455; -.
DR MIM; 608130; gene.
DR neXtProt; NX_O60285; -.
DR PharmGKB; PA142671242; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000004864; -.
DR HOVERGEN; HBG007160; -.
DR InParanoid; O60285; -.
DR KO; K08800; -.
DR OMA; NRPRPQY; -.
DR OrthoDB; EOG7MD4PN; -.
DR PhylomeDB; O60285; -.
DR SignaLink; O60285; -.
DR ChiTaRS; NUAK1; human.
DR GeneWiki; NUAK1; -.
DR GenomeRNAi; 9891; -.
DR NextBio; 37291; -.
DR PRO; PR:O60285; -.
DR ArrayExpress; O60285; -.
DR Bgee; O60285; -.
DR CleanEx; HS_NUAK1; -.
DR Genevestigator; O60285; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
DR GO; GO:2000772; P:regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0035507; P:regulation of myosin-light-chain-phosphatase activity; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Cell adhesion;
KW Complete proteome; Cytoplasm; DNA damage; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1 661 NUAK family SNF1-like kinase 1.
FT /FTId=PRO_0000086453.
FT DOMAIN 55 306 Protein kinase.
FT NP_BIND 61 69 ATP (By similarity).
FT MOTIF 399 402 GILK motif.
FT ACT_SITE 178 178 Proton acceptor (By similarity).
FT BINDING 84 84 ATP (Probable).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 22 22 Phosphoserine.
FT MOD_RES 211 211 Phosphothreonine; by LKB1.
FT MOD_RES 455 455 Phosphoserine.
FT MOD_RES 600 600 Phosphoserine; by PKB/AKT1.
FT VAR_SEQ 182 208 ENILLDDNCNIKIADFGLSNLYQKDKF -> KKTSRENQVT
FT TLPQSAVSLRSCWTVMM (in isoform 2).
FT /FTId=VSP_014236.
FT VAR_SEQ 209 661 Missing (in isoform 2).
FT /FTId=VSP_014237.
FT VARIANT 419 419 G -> D (in dbSNP:rs55774704).
FT /FTId=VAR_040963.
FT VARIANT 543 543 P -> R (in dbSNP:rs3741883).
FT /FTId=VAR_017246.
FT MUTAGEN 84 84 K->A: Abolishes kinase activity and
FT ability to induce senescence.
FT MUTAGEN 211 211 T->A: Prevents phosphorylation and
FT activation by STK11/LKB1 complex.
FT Abolishes ability to induce senescence.
FT MUTAGEN 400 401 IL->KK: Abolishes interaction with PPP1CB
FT and ability to regulate myosin PP1
FT activity.
FT MUTAGEN 600 600 S->A: Abrogates phosphorylation by
FT PKB/AKT1. Does not affect ability to
FT induce senescence.
FT CONFLICT 86 86 I -> V (in Ref. 3; BAB55026).
SQ SEQUENCE 661 AA; 74305 MW; 806F37D52CA4718F CRC64;
MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN LKHRYELQET
LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI RREIEIMSSL NHPHIISIYE
VFENKDKIVI IMEYASKGEL YDYISERRRL SERETRHFFR QIVSAVHYCH KNGVVHRDLK
LENILLDDNC NIKIADFGLS NLYQKDKFLQ TFCGSPLYAS PEIVNGRPYR GPEVDSWALG
VLLYTLVYGT MPFDGFDHKN LIRQISSGEY REPTQPSDAR GLIRWMLMVN PDRRATIEDI
ANHWWVNWGY KSSVCDCDAL HDSESPLLAR IIDWHHRSTG LQADTEAKMK GLAKPTTSEV
MLERQRSLKK SKKENDFAQS GQDAVPESPS KLSSKRPKGI LKKRSNSEHR SHSTGFIEGV
VGPALPSTFK MEQDLCRTGV LLPSSPEAEV PGKLSPKQSA TMPKKGILKK TQQRESGYYS
SPERSESSEL LDSNDVMGSS IPSPSPPDPA RVTSHSLSCR RKGILKHSSK YSAGTMDPAL
VSPEMPTLES LSEPGVPAEG LSRSYSRPSS VISDDSVLSS DSFDLLDLQE NRPARQRIRS
CVSAENFLQI QDFEGLQNRP RPQYLKRYRN RLADSSFSLL TDMDDVTQVY KQALEICSKL
N
//
MIM
608130
*RECORD*
*FIELD* NO
608130
*FIELD* TI
*608130 NUAK FAMILY, SNF1-LIKE KINASE, 1; NUAK1
;;AMPK-RELATED PROTEIN KINASE 5; ARK5;;
read moreKIAA0537
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned KIAA0537. The deduced 661-amino
acid protein shares about 52% identity over 252 amino acids with plant
SNF1-related protein kinase (605705). The KIAA0537 protein had an
apparent molecular mass of about 75 kD by SDS-PAGE. RT-PCR detected
highest expression in heart and brain, followed by skeletal muscle,
kidney, ovary, placenta, lung, and liver. Little to no expression was
detected in other tissues examined.
Suzuki et al. (2003) found that an antibody directed against SNARK
(608131) cross-reacted with a 74-kD protein that they called ARK5. By
screening databases, they determined that KIAA0537 and ARK5 are
identical. Overall, SNARK and ARK5 share 55% amino acid homology,
including 84% similarity within the N-terminal catalytic domains. ARK5
also shares significant homology with several other AMP-activated
protein kinases, including AMPK-alpha-1 (PRKAA1; 602739), AMPK-alpha-2
(PRKAA2; 600497), and MELK (607025).
GENE FUNCTION
By in vitro assay of ARK5 expressed by transfected HepG2 colon cancer
cells, Suzuki et al. (2003) demonstrated phosphorylation of a synthetic
test peptide. The phosphorylation was stimulated by AMP and did not
require accessory binding proteins. Transfection of ARK5 also increased
the survival of HepG2 cells exposed to glucose starvation and reduced
oxygen tension. Increased cell survival was accompanied by
phosphorylation of ARK5 on ser600 by AKT (see 164730), which activated
ARK5 kinase activity. Activated ARK5 phosphorylated ATM (607585), which
led to phosphorylation of p53 (191170). The authors proposed that ARK5
is a tumor cell survival factor that is activated by AKT and acts as an
ATM kinase under conditions of nutrient starvation.
Liu et al. (2012) showed in human and murine cell lines that oncogenic
levels of MYC (190080) establish a dependence on ARK5 for maintaining
metabolic homeostasis and for cell survival. ARK5 is an upstream
regulator of AMPK and limits protein synthesis via the mTOR complex-1
(see 601231) signaling pathway. ARK5 also maintains expression of
mitochondrial respiratory chain complexes and respiratory capacity,
which is required for efficient glutamine metabolism. Inhibition of ARK5
leads to a collapse of cellular ATP levels in cells expressing
deregulated MYC, inducing multiple proapoptotic responses as a secondary
consequence. Depletion of ARK5 prolonged survival in MYC-driven mouse
models of hepatocellular carcinoma, demonstrating that targeting
cellular energy homeostasis is a valid therapeutic strategy to eliminate
tumor cells that express deregulated MYC.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the NUAK1 gene
to chromosome 12.
*FIELD* RF
1. Liu, L.; Ulbrich, J.; Muller, J.; Wustefeld, T.; Aeberhard, L.;
Kress, T. R.; Muthalagu, N.; Rycak, L.; Rudalska, R.; Mull, R.; Kempa
S.; Zender, L.; Eilers, M.; Murphy, D. J.: Deregulated MYC expression
induces dependence upon AMPK-related kinase 5. Nature 483: 608-612,
2012.
2. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: 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: 31-39,
1998.
3. Suzuki, A.; Kusakai, G.; Kishimoto, A.; Lu, J.; Ogura, T.; Lavin,
M. F.; Esumi, H.: Identification of a novel protein kinase mediating
Akt survival signaling to the ATM protein. J. Biol. Chem. 278: 48-53,
2003.
*FIELD* CN
Ada Hamosh - updated: 5/15/2012
*FIELD* CD
Patricia A. Hartz: 9/29/2003
*FIELD* ED
alopez: 05/16/2012
alopez: 5/15/2012
terry: 5/15/2012
mgross: 9/29/2003
*RECORD*
*FIELD* NO
608130
*FIELD* TI
*608130 NUAK FAMILY, SNF1-LIKE KINASE, 1; NUAK1
;;AMPK-RELATED PROTEIN KINASE 5; ARK5;;
read moreKIAA0537
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned KIAA0537. The deduced 661-amino
acid protein shares about 52% identity over 252 amino acids with plant
SNF1-related protein kinase (605705). The KIAA0537 protein had an
apparent molecular mass of about 75 kD by SDS-PAGE. RT-PCR detected
highest expression in heart and brain, followed by skeletal muscle,
kidney, ovary, placenta, lung, and liver. Little to no expression was
detected in other tissues examined.
Suzuki et al. (2003) found that an antibody directed against SNARK
(608131) cross-reacted with a 74-kD protein that they called ARK5. By
screening databases, they determined that KIAA0537 and ARK5 are
identical. Overall, SNARK and ARK5 share 55% amino acid homology,
including 84% similarity within the N-terminal catalytic domains. ARK5
also shares significant homology with several other AMP-activated
protein kinases, including AMPK-alpha-1 (PRKAA1; 602739), AMPK-alpha-2
(PRKAA2; 600497), and MELK (607025).
GENE FUNCTION
By in vitro assay of ARK5 expressed by transfected HepG2 colon cancer
cells, Suzuki et al. (2003) demonstrated phosphorylation of a synthetic
test peptide. The phosphorylation was stimulated by AMP and did not
require accessory binding proteins. Transfection of ARK5 also increased
the survival of HepG2 cells exposed to glucose starvation and reduced
oxygen tension. Increased cell survival was accompanied by
phosphorylation of ARK5 on ser600 by AKT (see 164730), which activated
ARK5 kinase activity. Activated ARK5 phosphorylated ATM (607585), which
led to phosphorylation of p53 (191170). The authors proposed that ARK5
is a tumor cell survival factor that is activated by AKT and acts as an
ATM kinase under conditions of nutrient starvation.
Liu et al. (2012) showed in human and murine cell lines that oncogenic
levels of MYC (190080) establish a dependence on ARK5 for maintaining
metabolic homeostasis and for cell survival. ARK5 is an upstream
regulator of AMPK and limits protein synthesis via the mTOR complex-1
(see 601231) signaling pathway. ARK5 also maintains expression of
mitochondrial respiratory chain complexes and respiratory capacity,
which is required for efficient glutamine metabolism. Inhibition of ARK5
leads to a collapse of cellular ATP levels in cells expressing
deregulated MYC, inducing multiple proapoptotic responses as a secondary
consequence. Depletion of ARK5 prolonged survival in MYC-driven mouse
models of hepatocellular carcinoma, demonstrating that targeting
cellular energy homeostasis is a valid therapeutic strategy to eliminate
tumor cells that express deregulated MYC.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the NUAK1 gene
to chromosome 12.
*FIELD* RF
1. Liu, L.; Ulbrich, J.; Muller, J.; Wustefeld, T.; Aeberhard, L.;
Kress, T. R.; Muthalagu, N.; Rycak, L.; Rudalska, R.; Mull, R.; Kempa
S.; Zender, L.; Eilers, M.; Murphy, D. J.: Deregulated MYC expression
induces dependence upon AMPK-related kinase 5. Nature 483: 608-612,
2012.
2. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: 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: 31-39,
1998.
3. Suzuki, A.; Kusakai, G.; Kishimoto, A.; Lu, J.; Ogura, T.; Lavin,
M. F.; Esumi, H.: Identification of a novel protein kinase mediating
Akt survival signaling to the ATM protein. J. Biol. Chem. 278: 48-53,
2003.
*FIELD* CN
Ada Hamosh - updated: 5/15/2012
*FIELD* CD
Patricia A. Hartz: 9/29/2003
*FIELD* ED
alopez: 05/16/2012
alopez: 5/15/2012
terry: 5/15/2012
mgross: 9/29/2003