NUAK1_HUMAN
ID NUAK1_HUMAN Reviewed; 661 AA.
AC O60285; A7MD39; Q96KA8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 194.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ACTIVITY 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., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT 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. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., 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., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., 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., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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, AND
RP 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., Esumi H.;
RT "Identification of a novel protein kinase mediating Akt survival signaling
RT to the ATM protein.";
RL J. Biol. Chem. 278:48-53(2003).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14982852; DOI=10.1016/s0002-9440(10)63186-0;
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 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., Ogura T.,
RA 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., Shaughnessy J. Jr.,
RA Esumi H.;
RT "ARK5 is transcriptionally regulated by the Large-MAF family and mediates
RT IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular
RT 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 and
RT 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., Alessi D.R.;
RT "Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-
RT linked polyubiquitin chains.";
RL Biochem. J. 411:249-260(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-22; THR-211 AND SER-455, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Wang J.,
RA Martinez D., Abbadie C., Carling D., de Launoit Y., Gil J., Bernard D.;
RT "Regulation of ploidy and senescence by the AMPK-related kinase 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., Aizawa S.,
RA 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 FUNCTION, AND INTERACTION WITH CDKN1A.
RX PubMed=25329316; DOI=10.1371/journal.pgen.1004721;
RA Esteve-Puig R., Gil R., Gonzalez-Sanchez E., Bech-Serra J.J., Grueso J.,
RA Hernandez-Losa J., Moline T., Canals F., Ferrer B., Cortes J., Bastian B.,
RA Cajal S.R.Y., Martin-Caballero J., Flores J.M., Vivancos A.,
RA Garcia-Patos V., Recio J.A.;
RT "A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating
RT CDKN1A (p21WAF1/CIP1) degradation.";
RL PLoS Genet. 10:E1004721-E1004721(2014).
RN [20]
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., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA 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 processes
CC such as cell adhesion, regulation of cell ploidy and senescence, cell
CC proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1,
CC PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and
CC cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1,
CC thereby controlling its stability. Controls cell adhesion by regulating
CC activity of the myosin protein phosphatase 1 (PP1) complex. Acts by
CC mediating phosphorylation of PPP1R12A subunit of myosin PP1:
CC phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced
CC dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA
CC damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and
CC is recruited to the CDKN1A/WAF1 promoter to participate in
CC transcription activation by p53/TP53. May also act as a tumor
CC malignancy-associated factor by promoting tumor invasion and metastasis
CC under regulation and phosphorylation by AKT1. Suppresses Fas-induced
CC apoptosis by mediating phosphorylation of CASP6, thereby suppressing
CC the activation of the caspase and the subsequent cleavage of CFLAR.
CC Regulates UV radiation-induced DNA damage response mediated by CDKN1A.
CC In association with STK11, phosphorylates CDKN1A in response to UV
CC radiation and contributes to its degradation which is necessary for
CC optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306,
CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171,
CC ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127,
CC ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932,
CC ECO:0000269|PubMed:25329316}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-211. Activated
CC by phosphorylation at Ser-600 AKT1 during glucose starvation; the
CC relevance of such activation in normal cells is however unsure.
CC {ECO:0000269|PubMed:14976552}.
CC -!- SUBUNIT: Interacts (via GILK motif) with PPP1CB; the interaction is
CC direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.
CC {ECO:0000269|PubMed:25329316}.
CC -!- INTERACTION:
CC O60285; O95835: LATS1; NbExp=2; IntAct=EBI-1046789, EBI-444209;
CC O60285; Q9UQ35: SRRM2; NbExp=2; IntAct=EBI-1046789, EBI-1050142;
CC O60285; P04637: TP53; NbExp=5; IntAct=EBI-1046789, EBI-366083;
CC O60285; Q93008: USP9X; NbExp=2; IntAct=EBI-1046789, EBI-302524;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21317932}. Cytoplasm
CC {ECO:0000269|PubMed:21317932}.
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 -!- TISSUE SPECIFICITY: Expressed at high levels in heart and brain, and at
CC lower levels in skeletal muscle, kidney, ovary, placenta, lung and
CC liver. Highly up-regulated in colorectal cancer cell lines.
CC {ECO:0000269|PubMed:14982852}.
CC -!- INDUCTION: Transcriptionally regulated by members of the MAF family.
CC {ECO:0000269|PubMed:16044163, ECO:0000269|PubMed:16424013}.
CC -!- DOMAIN: The GILK motif mediates interaction with PPP1CB.
CC {ECO:0000269|PubMed:20354225}.
CC -!- PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins
CC which appear to impede LKB1-mediated phosphorylation. Deubiquitinated
CC by USP9X. {ECO:0000269|PubMed:18254724}.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-
CC 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 PP1
CC from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation
CC with IGF1. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:20354225}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25463.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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 CCDS; CCDS31892.1; -. [O60285-1]
DR RefSeq; NP_055655.1; NM_014840.2. [O60285-1]
DR AlphaFoldDB; O60285; -.
DR SMR; O60285; -.
DR BioGRID; 115221; 33.
DR IntAct; O60285; 65.
DR MINT; O60285; -.
DR STRING; 9606.ENSP00000261402; -.
DR BindingDB; O60285; -.
DR ChEMBL; CHEMBL5784; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O60285; -.
DR GuidetoPHARMACOLOGY; 2129; -.
DR iPTMnet; O60285; -.
DR PhosphoSitePlus; O60285; -.
DR BioMuta; NUAK1; -.
DR jPOST; O60285; -.
DR MassIVE; O60285; -.
DR PaxDb; O60285; -.
DR PeptideAtlas; O60285; -.
DR PRIDE; O60285; -.
DR ProteomicsDB; 49314; -. [O60285-1]
DR ProteomicsDB; 49315; -. [O60285-2]
DR Antibodypedia; 30646; 322 antibodies from 36 providers.
DR DNASU; 9891; -.
DR Ensembl; ENST00000261402.7; ENSP00000261402.2; ENSG00000074590.14. [O60285-1]
DR GeneID; 9891; -.
DR KEGG; hsa:9891; -.
DR MANE-Select; ENST00000261402.7; ENSP00000261402.2; NM_014840.3; NP_055655.1.
DR UCSC; uc001tlj.2; human. [O60285-1]
DR CTD; 9891; -.
DR DisGeNET; 9891; -.
DR GeneCards; NUAK1; -.
DR HGNC; HGNC:14311; NUAK1.
DR HPA; ENSG00000074590; Low tissue specificity.
DR MIM; 608130; gene.
DR neXtProt; NX_O60285; -.
DR OpenTargets; ENSG00000074590; -.
DR PharmGKB; PA142671242; -.
DR VEuPathDB; HostDB:ENSG00000074590; -.
DR eggNOG; KOG0611; Eukaryota.
DR GeneTree; ENSGT00940000157255; -.
DR HOGENOM; CLU_000288_63_42_1; -.
DR InParanoid; O60285; -.
DR OMA; PSPFKME; -.
DR PhylomeDB; O60285; -.
DR TreeFam; TF324572; -.
DR PathwayCommons; O60285; -.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; O60285; -.
DR SIGNOR; O60285; -.
DR BioGRID-ORCS; 9891; 14 hits in 1107 CRISPR screens.
DR ChiTaRS; NUAK1; human.
DR GeneWiki; NUAK1; -.
DR GenomeRNAi; 9891; -.
DR Pharos; O60285; Tchem.
DR PRO; PR:O60285; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O60285; protein.
DR Bgee; ENSG00000074590; Expressed in Brodmann (1909) area 23 and 204 other tissues.
DR ExpressionAtlas; O60285; baseline and differential.
DR Genevisible; O60285; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
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:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population 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 GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; Cytoplasm;
KW DNA damage; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1..661
FT /note="NUAK family SNF1-like kinase 1"
FT /id="PRO_0000086453"
FT DOMAIN 55..306
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 399..402
FT /note="GILK motif"
FT COMPBIAS 363..377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 61..69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 211
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000269|PubMed:14976552,
FT ECO:0000269|PubMed:20354225, ECO:0007744|PubMed:19369195"
FT MOD_RES 455
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 600
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:12409306"
FT VAR_SEQ 182..208
FT /note="ENILLDDNCNIKIADFGLSNLYQKDKF -> KKTSRENQVTTLPQSAVSLRS
FT CWTVMM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014236"
FT VAR_SEQ 209..661
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014237"
FT VARIANT 419
FT /note="G -> D (in dbSNP:rs55774704)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040963"
FT VARIANT 543
FT /note="P -> R (in dbSNP:rs3741883)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_017246"
FT MUTAGEN 84
FT /note="K->A: Abolishes kinase activity and ability to
FT induce senescence."
FT /evidence="ECO:0000269|PubMed:19927127,
FT ECO:0000269|PubMed:21317932"
FT MUTAGEN 211
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex. Abolishes ability to induce
FT senescence."
FT /evidence="ECO:0000269|PubMed:14976552,
FT ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:21317932"
FT MUTAGEN 400..401
FT /note="IL->KK: Abolishes interaction with PPP1CB and
FT ability to regulate myosin PP1 activity."
FT /evidence="ECO:0000269|PubMed:20354225"
FT MUTAGEN 600
FT /note="S->A: Abrogates phosphorylation by PKB/AKT1. Does
FT not affect ability to induce senescence."
FT /evidence="ECO:0000269|PubMed:12409306,
FT ECO:0000269|PubMed:19927127"
FT CONFLICT 86
FT /note="I -> V (in Ref. 3; BAB55026)"
FT /evidence="ECO:0000305"
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
