ID STK11_HUMAN Reviewed; 433 AA. AC Q15831; B2RBX7; E7EW76; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 237. DE RecName: Full=Serine/threonine-protein kinase STK11 {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:14976552}; DE AltName: Full=Liver kinase B1; DE Short=LKB1; DE Short=hLKB1; DE AltName: Full=Renal carcinoma antigen NY-REN-19; DE Flags: Precursor; GN Name=STK11 {ECO:0000312|HGNC:HGNC:11389}; Synonyms=LKB1, PJS; 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], AND INVOLVEMENT IN PJS. RC TISSUE=Liver; RX PubMed=9425897; DOI=10.1038/ng0198-38; RA Jenne D.E., Reimann H., Nezu J., Friedl W., Loff S., Jeschke R., RA Mueller O., Back W., Zimmer M.; RT "Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine RT kinase."; RL Nat. Genet. 18:38-43(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9537235; RA Bignell G.R., Barfoot R., Seal S., Collins N., Warren W., Stratton M.R.; RT "Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene RT in sporadic breast cancer."; RL Cancer Res. 58:1384-1386(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Uterus; 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 IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [8] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=11212897; DOI=10.1023/a:1006442024874; RA Sobottka S.B., Haase M., Fitze G., Hahn M., Schackert H.K., Schackert G.; RT "Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 RT mutations in human carcinoma metastases to the brain."; RL J. Neurooncol. 49:187-195(2000). RN [9] RP IDENTIFICATION IN A TERNARY COMPLEX COMPOSED OF SMAD4 AND STK11IP, AND RP INTERACTION WITH SMAD4 AND STK11IP. RX PubMed=11741830; DOI=10.1093/hmg/10.25.2869; RA Smith D.P., Rayter S.I., Niederlander C., Spicer J., Jones C.M., RA Ashworth A.; RT "LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers RT syndrome kinase LKB1."; RL Hum. Mol. Genet. 10:2869-2877(2001). RN [10] RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, FUNCTION, MUTAGENESIS OF LYS-78 RP AND THR-189, AND PHOSPHORYLATION AT THR-189. RX PubMed=11430832; DOI=10.1016/s1097-2765(01)00258-1; RA Karuman P., Gozani O., Odze R.D., Zhou X.C., Zhu H., Shaw R., Brien T.P., RA Bozzuto C.D., Ooi D., Cantley L.C., Yuan J.; RT "The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell RT death."; RL Mol. Cell 7:1307-1319(2001). RN [11] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=12097271; RA Sanchez-Cespedes M., Parrella P., Esteller M., Nomoto S., Trink B., RA Engles J.M., Westra W.H., Herman J.G., Sidransky D.; RT "Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the RT lung."; RL Cancer Res. 62:3659-3662(2002). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STRADA, PHOSPHORYLATION AT RP THR-336 AND THR-363, AND CHARACTERIZATION OF VARIANT SPORADIC CANCER RP TYR-176. RX PubMed=12805220; DOI=10.1093/emboj/cdg292; RA Baas A.F., Boudeau J., Sapkota G.P., Smit L., Medema R., Morrice N.A., RA Alessi D.R., Clevers H.C.; RT "Activation of the tumour suppressor kinase LKB1 by the STE20-like RT pseudokinase STRAD."; RL EMBO J. 22:3062-3072(2003). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-194, IDENTIFICATION IN A RP COMPLEX WITH STRADA AND CAB39, AND INTERACTION WITH STRADA; STRADB; CAB39 RP AND CAB39L. RX PubMed=14517248; DOI=10.1093/emboj/cdg490; RA Boudeau J., Baas A.F., Deak M., Morrice N.A., Kieloch A., Schutkowski M., RA Prescott A.R., Clevers H.C., Alessi D.R.; RT "MO25alpha/beta interact with STRADalpha/beta enhancing their ability to RT bind, activate and localize LKB1 in the cytoplasm."; RL EMBO J. 22:5102-5114(2003). RN [14] RP FUNCTION IN CELL POLARITY. RX PubMed=15016379; DOI=10.1016/s0092-8674(04)00114-x; RA Baas A.F., Kuipers J., van der Wel N.N., Batlle E., Koerten H.K., RA Peters P.J., Clevers H.C.; RT "Complete polarization of single intestinal epithelial cells upon RT activation of LKB1 by STRAD."; RL Cell 116:457-466(2004). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-194. 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 [16] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=15021901; DOI=10.1038/sj.onc.1207502; RA Carretero J., Medina P.P., Pio R., Montuenga L.M., Sanchez-Cespedes M.; RT "Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor RT suppressor gene."; RL Oncogene 23:4037-4040(2004). RN [17] RP FUNCTION. RX PubMed=15733851; DOI=10.1016/j.febslet.2005.01.042; RA Jaleel M., McBride A., Lizcano J.M., Deak M., Toth R., Morrice N.A., RA Alessi D.R.; RT "Identification of the sucrose non-fermenting related kinase SNRK, as a RT novel LKB1 substrate."; RL FEBS Lett. 579:1417-1423(2005). RN [18] RP FUNCTION, INTERACTION WITH PTEN, SUBCELLULAR LOCATION, AND CHARACTERIZATION RP OF VARIANT PJS ASN-176. RX PubMed=15987703; DOI=10.1093/hmg/ddi225; RA Mehenni H., Lin-Marq N., Buchet-Poyau K., Reymond A., Collart M.A., RA Picard D., Antonarakis S.E.; RT "LKB1 interacts with and phosphorylates PTEN: a functional link between two RT proteins involved in cancer predisposing syndromes."; RL Hum. Mol. Genet. 14:2209-2219(2005). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TP53. RX PubMed=17108107; DOI=10.1158/0008-5472.can-06-0999; RA Zeng P.Y., Berger S.L.; RT "LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate RT transcriptional activation."; RL Cancer Res. 66:10701-10708(2006). RN [20] RP INTERACTION WITH WDR6. RX PubMed=17216128; DOI=10.1007/s11010-006-9402-5; RA Xie X., Wang Z., Chen Y.; RT "Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell RT growth arrest and p27(Kip1) induction."; RL Mol. Cell. Biochem. 301:115-122(2007). RN [21] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=17711506; DOI=10.1111/j.1349-7006.2007.00585.x; RA Onozato R., Kosaka T., Achiwa H., Kuwano H., Takahashi T., Yatabe Y., RA Mitsudomi T.; RT "LKB1 gene mutations in Japanese lung cancer patients."; RL Cancer Sci. 98:1747-1751(2007). RN [22] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=17676035; DOI=10.1038/nature06030; RA Ji H., Ramsey M.R., Hayes D.N., Fan C., McNamara K., Kozlowski P., RA Torrice C., Wu M.C., Shimamura T., Perera S.A., Liang M.C., Cai D., RA Naumov G.N., Bao L., Contreras C.M., Li D., Chen L., Krishnamurthy J., RA Koivunen J., Chirieac L.R., Padera R.F., Bronson R.T., Lindeman N.I., RA Christiani D.C., Lin X., Shapiro G.I., Janne P.A., Johnson B.E., RA Meyerson M., Kwiatkowski D.J., Castrillon D.H., Bardeesy N., RA Sharpless N.E., Wong K.K.; RT "LKB1 modulates lung cancer differentiation and metastasis."; RL Nature 448:807-810(2007). RN [23] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=17384680; DOI=10.1038/sj.onc.1210418; RA Matsumoto S., Iwakawa R., Takahashi K., Kohno T., Nakanishi Y., Matsuno Y., RA Suzuki K., Nakamoto M., Shimizu E., Minna J.D., Yokota J.; RT "Prevalence and specificity of LKB1 genetic alterations in lung cancers."; RL Oncogene 26:5911-5918(2007). RN [24] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=18594528; DOI=10.1038/sj.bjc.6604469; RA Koivunen J.P., Kim J., Lee J., Rogers A.M., Park J.O., Zhao X., Naoki K., RA Okamoto I., Nakagawa K., Yeap B.Y., Meyerson M., Wong K.K., Richards W.G., RA Sugarbaker D.J., Johnson B.E., Janne P.A.; RT "Mutations in the LKB1 tumour suppressor are frequently detected in tumours RT from Caucasian but not Asian lung cancer patients."; RL Br. J. Cancer 99:245-252(2008). RN [25] RP RETRACTED PAPER. RX PubMed=18321849; DOI=10.1074/jbc.m708208200; RA Song P., Xie Z., Wu Y., Xu J., Dong Y., Zou M.H.; RT "Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases RT LKB1 nucleus export and apoptosis in endothelial cells."; RL J. Biol. Chem. 283:12446-12455(2008). RN [26] RP RETRACTION NOTICE OF PUBMED:18321849. RX PubMed=31519760; DOI=10.1074/jbc.w119.010661; RA Song P., Xie Z., Wu Y., Dong Y., Zou M.H.; RT "Withdrawal: Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation RT increases LKB1 nucleus export and apoptosis in endothelial cells."; RL J. Biol. Chem. 294:13831-13831(2019). RN [27] RP INTERACTION WITH SIRT1, ACETYLATION AT LYS-44; LYS-48; LYS-96; LYS-97; RP LYS-296; LYS-311; LYS-416; LYS-423 AND LYS-431, AND MUTAGENESIS OF LYS-44; RP LYS-48; LYS-96 AND LYS-97. RX PubMed=18687677; DOI=10.1074/jbc.m805711200; RA Lan F., Cacicedo J.M., Ruderman N., Ido Y.; RT "SIRT1 modulation of the acetylation status, cytosolic localization, and RT activity of LKB1. Possible role in AMP-activated protein kinase RT activation."; RL J. Biol. Chem. 283:27628-27635(2008). RN [28] RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, RP PHOSPHORYLATION AT SER-428, AND MUTAGENESIS OF SER-428. RX PubMed=18854309; DOI=10.1074/jbc.m806153200; RA Denison F.C., Hiscock N.J., Carling D., Woods A.; RT "Characterization of an alternative splice variant of LKB1."; RL J. Biol. Chem. 284:67-76(2009). RN [29] RP IDENTIFICATION BY MASS 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 [30] RP INVOLVEMENT IN LUNG CANCER. RX PubMed=20559149; DOI=10.1097/jto.0b013e3181e05016; RA Gao B., Sun Y., Zhang J., Ren Y., Fang R., Han X., Shen L., Liu X.Y., RA Pao W., Chen H., Ji H.; RT "Spectrum of LKB1, EGFR, and KRAS mutations in Chinese lung RT adenocarcinomas."; RL J. Thorac. Oncol. 5:1130-1135(2010). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP FUNCTION. 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 [33] RP REVIEW ON FUNCTION. RX PubMed=21396365; DOI=10.1016/j.febslet.2011.03.010; RA Alexander A., Walker C.L.; RT "The role of LKB1 and AMPK in cellular responses to stress and damage."; RL FEBS Lett. 585:952-957(2011). RN [34] RP REVIEW ON INVOLVEMENT IN LUNG CANCER. RX PubMed=21380642; DOI=10.1007/s13238-011-1021-6; RA Gao Y., Ge G., Ji H.; RT "LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor RT suppressor."; RL Protein Cell 2:99-107(2011). RN [35] RP ACTIVITY REGULATION, INTERACTION WITH NR4A1, AND SUBCELLULAR LOCATION. RX PubMed=22983157; DOI=10.1038/nchembio.1069; RA Zhan Y.Y., Chen Y., Zhang Q., Zhuang J.J., Tian M., Chen H.Z., Zhang L.R., RA Zhang H.K., He J.P., Wang W.J., Wu R., Wang Y., Shi C., Yang K., Li A.Z., RA Xin Y.Z., Li T.Y., Yang J.Y., Zheng Z.H., Yu C.D., Lin S.C., Chang C., RA Huang P.Q., Lin T., Wu Q.; RT "The orphan nuclear receptor Nur77 regulates LKB1 localization and RT activates AMPK."; RL Nat. Chem. Biol. 8:897-904(2012). RN [36] RP INTERACTION WITH NISCH, AND SUBCELLULAR LOCATION. RX PubMed=23572524; DOI=10.1074/jbc.m112.418103; RA Jain P., Baranwal S., Dong S., Struckhoff A.P., Worthylake R.A., RA Alahari S.K.; RT "Integrin-binding protein nischarin interacts with tumor suppressor liver RT kinase B1 (LKB1) to regulate cell migration of breast epithelial cells."; RL J. Biol. Chem. 288:15495-15509(2013). RN [37] RP SUBCELLULAR LOCATION (ISOFORM 2), AND PHOSPHORYLATION AT SER-399 (ISOFORM RP 2). RX PubMed=23612973; DOI=10.1074/jbc.m112.443580; RA Zhu H., Moriasi C.M., Zhang M., Zhao Y., Zou M.H.; RT "Phosphorylation of serine 399 in LKB1 protein short form by protein kinase RT Czeta is required for its nucleocytoplasmic transport and consequent AMP- RT activated protein kinase (AMPK) activation."; RL J. Biol. Chem. 288:16495-16505(2013). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31 AND SER-401, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [39] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [40] 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 [41] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 43-347 IN COMPLEX WITH STRADA AND RP CAB39, ACTIVITY REGULATION, CHARACTERIZATION OF VARIANTS SPORADIC CANCER RP MET-66; GLY-86; ARG-123; SER-157; ASP-163; PRO-170; SER-171; ARG-174; RP TYR-176; ASN-177; GLU-181; GLN-199; THR-205; PHE-216; VAL-223; PRO-230; RP PRO-232; ARG-245; PRO-250; HIS-272; TYR-277; GLN-285 AND SER-315, AND RP MUTAGENESIS OF ARG-74; ASP-194 AND PHE-204. RX PubMed=19892943; DOI=10.1126/science.1178377; RA Zeqiraj E., Filippi B.M., Deak M., Alessi D.R., van Aalten D.M.; RT "Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism RT of kinase activation."; RL Science 326:1707-1711(2009). RN [42] RP VARIANTS PJS 50-LEU--ASP-53 DEL; ASN-176 AND CYS-308, CHARACTERIZATION OF RP VARIANTS PJS PRO-67; ASN-176 AND CYS-308, AND MUTAGENESIS OF LYS-78. RX PubMed=9837816; DOI=10.1086/302159; RA Mehenni H., Gehrig C., Nezu J., Oku A., Shimane M., Rossier C., Guex N., RA Blouin J.L., Scott H.S., Antonarakis S.E.; RT "Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for RT allelic and locus heterogeneity."; RL Am. J. Hum. Genet. 63:1641-1650(1998). RN [43] RP VARIANT TGCT ASP-163. RX PubMed=9605748; RA Avizienyte E., Roth S., Loukola A., Hemminki A., Lothe R.A., Stenwig A.E., RA Fossaa S.D., Salovaara R., Aaltonen L.A.; RT "Somatic mutations in LKB1 are rare in sporadic colorectal and testicular RT tumors."; RL Cancer Res. 58:2087-2090(1998). RN [44] RP VARIANTS COLORECTAL CANCER SER-171; LYS-199; ASN-208; ASP-215; LEU-354 AND RP MET-367. RX PubMed=9731485; RA Dong S.M., Kim K.M., Kim S.Y., Shin M.S., Na E.Y., Lee S.H., Park W.S., RA Yoo N.J., Jang J.J., Yoon C.Y., Kim J.W., Kim S.Y., Yang Y.M., Kim S.H., RA Kim C.S., Lee J.Y.; RT "Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers RT syndrome gene in left-sided colon cancer."; RL Cancer Res. 58:3787-3790(1998). RN [45] RP VARIANT COLORECTAL CANCER HIS-314. RX PubMed=9809980; RA Resta N., Simone C., Mareni C., Montera M., Gentile M., Susca F., RA Gristina R., Pozzi S., Bertario L., Bufo P., Carlomagno N., Ingrosso M., RA Rossini F.P., Tenconi R., Guanti G.; RT "STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer."; RL Cancer Res. 58:4799-4801(1998). RN [46] RP VARIANT PJS ASN-247 DEL. RX PubMed=9760200; DOI=10.1007/s004390050801; RA Nakagawa H., Koyama K., Miyoshi Y., Ando H., Baba S., Watatani M., RA Yasutomi M., Matsuura N., Monden M., Nakamura Y.; RT "Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers RT syndrome."; RL Hum. Genet. 103:168-172(1998). RN [47] RP VARIANT GASTRIC CARCINOMA LEU-324. RX PubMed=9683800; RA Park W.S., Moon Y.W., Yang Y.M., Kim Y.S., Kim Y.D., Fuller B.G., RA Vortmeyer A.O., Fogt F., Lubensky I.A., Zhuang Z.; RT "Mutations of the STK11 gene in sporadic gastric carcinoma."; RL Int. J. Oncol. 13:601-604(1998). RN [48] RP VARIANTS PJS PRO-67 AND 303-ILE--GLN-306 DELINS ASN. RX PubMed=9428765; DOI=10.1038/34432; RA Hemminki A., Markie D., Tomlinson I., Avizienyte E., Roth S., Loukola A., RA Bignell G., Warren W., Aminoff M., Hoeglund P., Jaervinen H., Kristo P., RA Pelin K., Ridanpaeae M., Salovaara R., Toro T., Bodmer W., Olschwang S., RA Olsen A.S., Stratton M.R., de la Chapelle A., Aaltonen L.A.; RT "A serine/threonine kinase gene defective in Peutz-Jeghers syndrome."; RL Nature 391:184-187(1998). RN [49] RP VARIANT LUNG CANCER VAL-194. RX PubMed=10079245; DOI=10.1016/s0002-9440(10)65314-x; RA Avizienyte E., Loukola A., Roth S., Hemminki A., Tarkkanen M., RA Salovaara R., Arola J., Butzow R., Husgafvel-Pursiainen K., Kokkola A., RA Jarvinen H., Aaltonen L.A.; RT "LKB1 somatic mutations in sporadic cancers."; RL Am. J. Pathol. 154:677-681(1999). RN [50] RP VARIANTS PJS 162-ASP--LEU-164 DELINS ASN-ASP-MET; ASN-194 AND LYS-297. RX PubMed=10408777; RX DOI=10.1002/(sici)1098-1004(1999)13:6<476::aid-humu7>3.0.co;2-2; RA Westerman A.M., Entius M.M., Boor P.P.C., Koole R., de Baar E., RA Offerhaus G.J.A., Lubinski J., Lindhout D., Halley D.J.J., de Rooij F.W.M., RA Wilson J.H.P.; RT "Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families."; RL Hum. Mutat. 13:476-481(1999). RN [51] RP CHARACTERIZATION OF VARIANT TGCT ASP-163. RX PubMed=9887330; DOI=10.1093/hmg/8.1.45; RA Ylikorkala A., Avizienyte E., Tomlinson I.P., Tiainen M., Roth S., RA Loukola A., Hemminki A., Johansson M., Sistonen P., Markie D., Neale K., RA Phillips R., Zauber P., Twama T., Sampson J., Jaervinen H., Maekelae T.P., RA Aaltonen L.A.; RT "Mutations and impaired function of LKB1 in familial and non-familial RT Peutz-Jeghers syndrome and a sporadic testicular cancer."; RL Hum. Mol. Genet. 8:45-51(1999). RN [52] RP VARIANT OVARIAN CARCINOMA LEU-281. RX PubMed=10429654; DOI=10.1111/j.1349-7006.1999.tb00793.x; RA Nishioka Y., Kobayashi K., Sagae S., Sugimura M., Ishioka S., Nagata M., RA Terasawa K., Tokino T., Kudo R.; RT "Mutational analysis of STK11 gene in ovarian carcinomas."; RL Jpn. J. Cancer Res. 90:629-632(1999). RN [53] RP VARIANTS MELANOMA ASP-49 AND ARG-135. RX PubMed=10201537; DOI=10.1046/j.1523-1747.1999.00551.x; RA Rowan A., Bataille V., MacKie R., Healy E., Bicknell D., Bodmer W., RA Tomlinson I.; RT "Somatic mutations in the Peutz-Jeghers (LKB1/STKII) gene in sporadic RT malignant melanomas."; RL J. Invest. Dermatol. 112:509-511(1999). RN [54] RP VARIANT MELANOMA TYR-194. RX PubMed=10208439; DOI=10.1038/sj.onc.1202486; RA Guldberg P., thor Straten P., Ahrenkiel V., Seremet T., Kirkin A.F., RA Zeuthen J.; RT "Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in RT malignant melanoma."; RL Oncogene 18:1777-1780(1999). RN [55] RP VARIANTS PJS CYS-239 AND SER-315. RX PubMed=12372054; DOI=10.1034/j.1399-0004.2002.620405.x; RA Scott R.J., Crooks R., Meldrum C.J., Thomas L., Smith C.J.A., Mowat D., RA McPhillips M., Spigelman A.D.; RT "Mutation analysis of the STK11/LKB1 gene and clinical characteristics of RT an Australian series of Peutz-Jeghers syndrome patients."; RL Clin. Genet. 62:282-287(2002). RN [56] RP VARIANTS CERVICAL CANCER LYS-14; PRO-160 AND LEU-231, AND VARIANT CERVICAL RP CARCINOMA MET-66. RX PubMed=12533684; DOI=10.1097/01.lab.0000049821.16698.d0; RA Kuragaki C., Enomoto T., Ueno Y., Sun H., Fujita M., Nakashima R., Ueda Y., RA Wada H., Murata Y., Toki T., Konishi I., Fujii S.; RT "Mutations in the STK11 gene characterize minimal deviation adenocarcinoma RT of the uterine cervix."; RL Lab. Invest. 83:35-45(2003). RN [57] RP VARIANT [LARGE SCALE ANALYSIS] LYS-87. 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). RN [58] RP VARIANT PJS GLY-16. RX PubMed=21411391; DOI=10.1016/j.clinre.2010.11.008; RA Liu L., Du X., Nie J.; RT "A novel de novo mutation in LKB1 gene in a Chinese Peutz Jeghers syndrome RT patient significantly diminished p53 activity."; RL Clin. Res. Hepatol. Gastroenterol. 35:221-226(2011). CC -!- FUNCTION: Tumor suppressor serine/threonine-protein kinase that CC controls the activity of AMP-activated protein kinase (AMPK) family CC members, thereby playing a role in various processes such as cell CC metabolism, cell polarity, apoptosis and DNA damage response. Acts by CC phosphorylating the T-loop of AMPK family proteins, thus promoting CC their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, CC MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not CC MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN CC and possibly p53/TP53. Acts as a key upstream regulator of AMPK by CC mediating phosphorylation and activation of AMPK catalytic subunits CC PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition CC of signaling pathways that promote cell growth and proliferation when CC energy levels are low, glucose homeostasis in liver, activation of CC autophagy when cells undergo nutrient deprivation, and B-cell CC differentiation in the germinal center in response to DNA damage. Also CC acts as a regulator of cellular polarity by remodeling the actin CC cytoskeleton. Required for cortical neuron polarization by mediating CC phosphorylation and activation of BRSK1 and BRSK2, leading to axon CC initiation and specification. Involved in DNA damage response: CC interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to CC participate in transcription activation. Able to phosphorylate CC p53/TP53; the relevance of such result in vivo is however unclear and CC phosphorylation may be indirect and mediated by downstream STK11/LKB1 CC kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis CC via interaction with p53/TP53: translocates to the mitochondrion during CC apoptosis and regulates p53/TP53-dependent apoptosis pathways. CC Regulates UV radiation-induced DNA damage response mediated by CDKN1A. CC In association with NUAK1, 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:11430832, CC ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, CC ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, CC ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, CC ECO:0000269|PubMed:25329316}. CC -!- FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}. 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 Evidence={ECO:0000269|PubMed:14976552}; 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; Evidence={ECO:0000269|PubMed:14976552}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC -!- ACTIVITY REGULATION: Activated by forming a complex with STRAD (STRADA CC or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA CC (or STRADB)-binding promotes a conformational change of STK11/LKB1 in CC an active conformation, which is stabilized by CAB39/MO25alpha (or CC CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. CC Sequestration in the nucleus by NR4A1 prevents it from phosphorylating CC and activating cytoplasmic AMPK. {ECO:0000269|PubMed:19892943, CC ECO:0000269|PubMed:22983157}. CC -!- SUBUNIT: Catalytic component of a trimeric complex composed of CC STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CC CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and CC stimulates its catalytic activity. Found in a ternary complex composed CC of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, CC STK11IP and WDR6. Interacts with NR4A1. Interacts with NISCH; this CC interaction may increase STK11 activity. Interacts with PTEN; leading CC to PTEN phosphorylation. Interacts with SIRT1; the interaction CC deacetylates STK11. Interacts with CDKN1A. CC {ECO:0000269|PubMed:11741830, ECO:0000269|PubMed:12805220, CC ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:15987703, CC ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:17216128, CC ECO:0000269|PubMed:18687677, ECO:0000269|PubMed:19892943, CC ECO:0000269|PubMed:22983157, ECO:0000269|PubMed:23572524, CC ECO:0000269|PubMed:25329316}. CC -!- INTERACTION: CC Q15831; Q9Y376: CAB39; NbExp=16; IntAct=EBI-306838, EBI-306905; CC Q15831; Q16543: CDC37; NbExp=5; IntAct=EBI-306838, EBI-295634; CC Q15831; Q9BT78: COPS4; NbExp=4; IntAct=EBI-306838, EBI-742413; CC Q15831; Q13451: FKBP5; NbExp=7; IntAct=EBI-306838, EBI-306914; CC Q15831; P07900: HSP90AA1; NbExp=3; IntAct=EBI-306838, EBI-296047; CC Q15831; P08238: HSP90AB1; NbExp=5; IntAct=EBI-306838, EBI-352572; CC Q15831; O95835: LATS1; NbExp=2; IntAct=EBI-306838, EBI-444209; CC Q15831; Q96L34: MARK4; NbExp=2; IntAct=EBI-306838, EBI-302319; CC Q15831; P26927: MST1; NbExp=2; IntAct=EBI-306838, EBI-6929133; CC Q15831; P54646: PRKAA2; NbExp=3; IntAct=EBI-306838, EBI-1383852; CC Q15831; Q7RTN6: STRADA; NbExp=16; IntAct=EBI-306838, EBI-1109114; CC Q15831; Q7RTN6-1: STRADA; NbExp=3; IntAct=EBI-306838, EBI-15787241; CC Q15831; Q9C0K7: STRADB; NbExp=9; IntAct=EBI-306838, EBI-306893; CC Q15831; Q8NFZ5: TNIP2; NbExp=5; IntAct=EBI-306838, EBI-359372; CC Q15831; Q9NNW5: WDR6; NbExp=3; IntAct=EBI-306838, EBI-1568315; CC Q15831; P63104: YWHAZ; NbExp=6; IntAct=EBI-306838, EBI-347088; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Membrane {ECO:0000250}. CC Mitochondrion. Note=A small fraction localizes at membranes (By CC similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or CC STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). CC Translocates to the mitochondrion during apoptosis. PTEN promotes CC cytoplasmic localization. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus CC {ECO:0000269|PubMed:23612973}. Cytoplasm {ECO:0000269|PubMed:23612973}. CC Note=Predominantly nuclear, but translocates to the cytoplasm in CC response to metformin or peroxynitrite treatment. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=LKB1(L); CC IsoId=Q15831-1; Sequence=Displayed; CC Name=2; Synonyms=LKB1(S); CC IsoId=Q15831-2; Sequence=VSP_041746; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Strongest expression in CC testis and fetal liver. CC -!- PTM: Phosphorylated by ATM at Thr-363 following ionizing radiation CC (IR). Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required CC to inhibit cell growth. Phosphorylation at Ser-428 is also required CC during neuronal polarization to mediate phosphorylation of BRSK1 and CC BRSK2 (By similarity). Phosphorylation by PKC/PRKCZ at Ser-399 in CC isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export CC of STK11 and activation of AMPK. UV radiation-induced phosphorylation CC at Thr-363 mediates CDKN1A degradation (By similarity). CC {ECO:0000250|UniProtKB:Q9WTK7, ECO:0000269|PubMed:11430832, CC ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:18854309}. CC -!- PTM: Acetylated. Deacetylation at Lys-48 enhances cytoplasmic CC localization and kinase activity in vitro. CC {ECO:0000269|PubMed:18687677}. CC -!- DISEASE: Peutz-Jeghers syndrome (PJS) [MIM:175200]: An autosomal CC dominant disorder characterized by melanocytic macules of the lips, CC multiple gastrointestinal hamartomatous polyps and an increased risk CC for various neoplasms, including gastrointestinal cancer. CC {ECO:0000269|PubMed:10408777, ECO:0000269|PubMed:12372054, CC ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:21411391, CC ECO:0000269|PubMed:9425897, ECO:0000269|PubMed:9428765, CC ECO:0000269|PubMed:9760200, ECO:0000269|PubMed:9837816}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common CC malignancy in males representing 95% of all testicular neoplasms. TGCTs CC have various pathologic subtypes including: unclassified intratubular CC germ cell neoplasia, seminoma (including cases with CC syncytiotrophoblastic cells), spermatocytic seminoma, embryonal CC carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. CC {ECO:0000269|PubMed:9605748, ECO:0000269|PubMed:9887330}. Note=The gene CC represented in this entry may be involved in disease pathogenesis. CC -!- DISEASE: Note=Defects in STK11 are associated with some sporadic CC cancers, especially lung cancers. Frequently mutated and inactivated in CC non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis CC process, especially lung cancer progression and metastasis. Confers CC lung adenocarcinoma the ability to trans-differentiate into squamous CC cell carcinoma. Also able to promote lung cancer metastasis, via both CC cancer-cell autonomous and non-cancer-cell autonomous mechanisms. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. LKB1 subfamily. {ECO:0000305}. CC -!- CAUTION: Its phosphorylation by PKC/PRKCZ at Ser-428 is reported to CC promote peroxynitrite-induced nuclear export of STK11, leading to PTEN CC activation and subsequent inhibition of PI3K/AKT signaling and CC induction of apoptosis in vein endothelial cells (PubMed:18321849). CC However this paper was withdrawn by the authors due to concerns of CC image duplication in the figures. Its phosphorylation by PKC/PRKCZ has CC been confirmed in other studies (PubMed:18854309, PubMed:23612973). CC {ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:18854309, CC ECO:0000269|PubMed:23612973, ECO:0000305|PubMed:31519760}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/292/STK11"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=PJS entry; CC URL="https://en.wikipedia.org/wiki/PJS"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U63333; AAB05809.1; -; mRNA. DR EMBL; AF035625; AAC39527.1; -; mRNA. DR EMBL; AF032984; AAB97833.1; -; Genomic_DNA. DR EMBL; AF055327; AAC15742.1; -; Genomic_DNA. DR EMBL; AF055320; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055321; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055322; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055323; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055324; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055325; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AF055326; AAC15742.1; JOINED; Genomic_DNA. DR EMBL; AK314858; BAG37374.1; -; mRNA. DR EMBL; AC011544; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004221; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471139; EAW69540.1; -; Genomic_DNA. DR EMBL; BC007981; AAH07981.1; -; mRNA. DR EMBL; BC019334; AAH19334.1; -; mRNA. DR CCDS; CCDS45896.1; -. [Q15831-1] DR RefSeq; NP_000446.1; NM_000455.4. [Q15831-1] DR RefSeq; XP_005259675.1; XM_005259618.3. DR PDB; 2WTK; X-ray; 2.65 A; C/F=43-347. DR PDB; 4ZDR; X-ray; 2.90 A; A/B=333-340. DR PDB; 5WXN; X-ray; 2.93 A; C/D=331-343. DR PDBsum; 2WTK; -. DR PDBsum; 4ZDR; -. DR PDBsum; 5WXN; -. DR AlphaFoldDB; Q15831; -. DR SMR; Q15831; -. DR BioGRID; 112670; 316. DR ComplexPortal; CPX-2431; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39L-STRADA variant. DR ComplexPortal; CPX-2845; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39-STRADA variant. DR ComplexPortal; CPX-2868; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39-STRADB variant. DR ComplexPortal; CPX-2869; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39L-STRADB variant. DR CORUM; Q15831; -. DR DIP; DIP-31317N; -. DR IntAct; Q15831; 146. DR MINT; Q15831; -. DR STRING; 9606.ENSP00000324856; -. DR BindingDB; Q15831; -. DR ChEMBL; CHEMBL5606; -. DR DrugCentral; Q15831; -. DR GlyGen; Q15831; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15831; -. DR PhosphoSitePlus; Q15831; -. DR BioMuta; STK11; -. DR DMDM; 3024670; -. DR CPTAC; CPTAC-2999; -. DR CPTAC; CPTAC-3000; -. DR EPD; Q15831; -. DR jPOST; Q15831; -. DR MassIVE; Q15831; -. DR MaxQB; Q15831; -. DR PaxDb; 9606-ENSP00000324856; -. DR PeptideAtlas; Q15831; -. DR ProteomicsDB; 60780; -. [Q15831-1] DR ProteomicsDB; 60781; -. [Q15831-2] DR Pumba; Q15831; -. DR Antibodypedia; 2048; 1501 antibodies from 44 providers. DR DNASU; 6794; -. DR Ensembl; ENST00000326873.12; ENSP00000324856.6; ENSG00000118046.17. [Q15831-1] DR Ensembl; ENST00000585465.3; ENSP00000490268.2; ENSG00000118046.17. [Q15831-2] DR Ensembl; ENST00000652231.1; ENSP00000498804.1; ENSG00000118046.17. [Q15831-2] DR GeneID; 6794; -. DR KEGG; hsa:6794; -. DR MANE-Select; ENST00000326873.12; ENSP00000324856.6; NM_000455.5; NP_000446.1. DR UCSC; uc002lrl.2; human. [Q15831-1] DR AGR; HGNC:11389; -. DR CTD; 6794; -. DR DisGeNET; 6794; -. DR GeneCards; STK11; -. DR GeneReviews; STK11; -. DR HGNC; HGNC:11389; STK11. DR HPA; ENSG00000118046; Low tissue specificity. DR MalaCards; STK11; -. DR MIM; 175200; phenotype. DR MIM; 273300; phenotype. DR MIM; 602216; gene. DR neXtProt; NX_Q15831; -. DR OpenTargets; ENSG00000118046; -. DR Orphanet; 2869; Peutz-Jeghers syndrome. DR PharmGKB; PA36198; -. DR VEuPathDB; HostDB:ENSG00000118046; -. DR eggNOG; KOG0583; Eukaryota. DR GeneTree; ENSGT00940000158050; -. DR HOGENOM; CLU_000288_1_2_1; -. DR InParanoid; Q15831; -. DR OMA; AYHYGSE; -. DR OrthoDB; 5489318at2759; -. DR PhylomeDB; Q15831; -. DR TreeFam; TF105322; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; Q15831; -. DR Reactome; R-HSA-163680; AMPK inhibits chREBP transcriptional activation activity. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-9614657; FOXO-mediated transcription of cell death genes. DR SignaLink; Q15831; -. DR SIGNOR; Q15831; -. DR BioGRID-ORCS; 6794; 153 hits in 1229 CRISPR screens. DR ChiTaRS; STK11; human. DR EvolutionaryTrace; Q15831; -. DR GeneWiki; STK11; -. DR GenomeRNAi; 6794; -. DR Pharos; Q15831; Tchem. DR PRO; PR:Q15831; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q15831; Protein. DR Bgee; ENSG00000118046; Expressed in left testis and 156 other cell types or tissues. DR ExpressionAtlas; Q15831; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0140535; C:intracellular protein-containing complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:1902554; C:serine/threonine protein kinase complex; IPI:ComplexPortal. DR GO; GO:0030018; C:Z disc; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0030275; F:LRR domain binding; IEA:Ensembl. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0002039; F:p53 binding; IDA:UniProtKB. DR GO; GO:0030295; F:protein kinase activator activity; IDA: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:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0032147; P:activation of protein kinase activity; IDA:MGI. DR GO; GO:0043276; P:anoikis; IMP:BHF-UCL. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0071493; P:cellular response to UV-B; IDA:UniProtKB. DR GO; GO:0097484; P:dendrite extension; IEA:Ensembl. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IEA:Ensembl. DR GO; GO:0030010; P:establishment of cell polarity; IMP:UniProtKB. DR GO; GO:0070314; P:G1 to G0 transition; IDA:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0051645; P:Golgi localization; IEA:Ensembl. DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IDA:UniProtKB. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:ParkinsonsUK-UCL. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl. DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:1901610; P:positive regulation of vesicle transport along microtubule; IMP:UniProtKB. DR GO; GO:0045059; P:positive thymic T cell selection; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; TAS:Reactome. DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB. DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome. DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl. DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB. DR GO; GO:0033993; P:response to lipid; IEA:Ensembl. DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0001894; P:tissue homeostasis; IEA:Ensembl. DR GO; GO:0001944; P:vasculature development; ISS:UniProtKB. DR CDD; cd14119; STKc_LKB1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00613; -. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR039154; LKB1_c. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR43895; CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE KINASE-RELATED; 1. DR PANTHER; PTHR43895:SF25; SERINE_THREONINE-PROTEIN KINASE STK11; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q15831; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; KW Autophagy; Cell cycle; Cytoplasm; Differentiation; Disease variant; KW DNA damage; Kinase; Lipoprotein; Magnesium; Manganese; Membrane; KW Metal-binding; Methylation; Mitochondrion; Nucleotide-binding; Nucleus; KW Palmitate; Phosphoprotein; Prenylation; Reference proteome; KW Serine/threonine-protein kinase; Spermatogenesis; Transferase; KW Tumor suppressor. FT CHAIN 1..430 FT /note="Serine/threonine-protein kinase STK11" FT /id="PRO_0000086699" FT PROPEP 431..433 FT /note="Removed in mature form" FT /evidence="ECO:0000250" FT /id="PRO_0000422300" FT DOMAIN 49..309 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 45..90 FT /note="Sufficient for interaction with SIRT1" FT /evidence="ECO:0000269|PubMed:18687677" FT REGION 312..331 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 397..433 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 176 FT /note="Proton acceptor" FT BINDING 55..63 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 78 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT MOD_RES 31 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 44 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 48 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 96 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 97 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 189 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11430832" FT MOD_RES 296 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 311 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 325 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WTK7" FT MOD_RES 336 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12805220" FT MOD_RES 363 FT /note="Phosphothreonine; by ATM and autocatalysis" FT /evidence="ECO:0000269|PubMed:12805220" FT MOD_RES 401 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 416 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 423 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT MOD_RES 428 FT /note="Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and FT RPS6KA1" FT /evidence="ECO:0000269|PubMed:18854309" FT MOD_RES 430 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000250" FT MOD_RES 431 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:18687677" FT LIPID 418 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 430 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000250" FT VAR_SEQ 371..433 FT /note="QVPEEEASHNGQRRGLPKAVCMNGTEAAQLSTKSRAEGRAPNPARKACSASS FT KIRRLSACKQQ -> GEEASEAGLRAERGLQKSEGSDLSGEEASRPAPQ (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_041746" FT VARIANT 14 FT /note="E -> K (in cervical cancer; somatic mutation)" FT /evidence="ECO:0000269|PubMed:12533684" FT /id="VAR_065627" FT VARIANT 16 FT /note="E -> G (in PJS)" FT /evidence="ECO:0000269|PubMed:21411391" FT /id="VAR_065628" FT VARIANT 49 FT /note="Y -> D (in melanoma; sporadic malignant; somatic FT mutation; dbSNP:rs137853080)" FT /evidence="ECO:0000269|PubMed:10201537" FT /id="VAR_033138" FT VARIANT 50..53 FT /note="Missing (in PJS)" FT /evidence="ECO:0000269|PubMed:9837816" FT /id="VAR_071057" FT VARIANT 66 FT /note="V -> M (in cervical carcinoma; somatic mutation; FT dbSNP:rs1599915144)" FT /evidence="ECO:0000269|PubMed:12533684, FT ECO:0000269|PubMed:19892943" FT /id="VAR_065629" FT VARIANT 67 FT /note="L -> P (in PJS; abolishes kinase activity, leading FT to loss of autophosphorylation; dbSNP:rs137853077)" FT /evidence="ECO:0000269|PubMed:9428765, FT ECO:0000269|PubMed:9837816" FT /id="VAR_006202" FT VARIANT 86 FT /note="R -> G (in sporadic cancer; somatic mutation; no FT effect on kinase activity nor in heterotrimeric complex FT assembly with STRADA and CAB39; dbSNP:rs1057520039)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065630" FT VARIANT 87 FT /note="R -> K (in a metastatic melanoma sample; somatic FT mutation; dbSNP:rs1568690463)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041139" FT VARIANT 123 FT /note="Q -> R (in sporadic cancer; somatic mutation; no FT effect on kinase activity nor in heterotrimeric complex FT assembly with STRADA and CAB39; dbSNP:rs764449808)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065631" FT VARIANT 135 FT /note="G -> R (in melanoma; sporadic malignant; somatic FT mutation; dbSNP:rs137853081)" FT /evidence="ECO:0000269|PubMed:10201537" FT /id="VAR_033139" FT VARIANT 157 FT /note="F -> S (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065632" FT VARIANT 160 FT /note="L -> P (in cervical cancer; somatic mutation)" FT /evidence="ECO:0000269|PubMed:12533684" FT /id="VAR_065633" FT VARIANT 162..164 FT /note="DGL -> NDM (in PJS)" FT /evidence="ECO:0000269|PubMed:10408777" FT /id="VAR_007920" FT VARIANT 163 FT /note="G -> D (in TGCT; a tumor with seminoma and teratoma FT components; somatic mutation; severely impaired but FT detectable kinase activity; impairs heterotrimeric complex FT assembly with STRADA and CAB39; predominantly nuclear FT localization; dbSNP:rs137853078)" FT /evidence="ECO:0000269|PubMed:19892943, FT ECO:0000269|PubMed:9605748, ECO:0000269|PubMed:9887330" FT /id="VAR_033140" FT VARIANT 170 FT /note="Q -> P (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065634" FT VARIANT 171 FT /note="G -> S (in colorectal cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39; dbSNP:rs1599926499)" FT /evidence="ECO:0000269|PubMed:19892943, FT ECO:0000269|PubMed:9731485" FT /id="VAR_065635" FT VARIANT 174 FT /note="H -> R (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065636" FT VARIANT 176 FT /note="D -> N (in PJS; loss of kinase activity, leading to FT greatly reduced autophosphorylation; fails to phosphorylate FT PTEN in vitro; no significant effect on nucleocytoplasmic FT localization; dbSNP:rs730881979)" FT /evidence="ECO:0000269|PubMed:15987703, FT ECO:0000269|PubMed:9837816" FT /id="VAR_071058" FT VARIANT 176 FT /note="D -> Y (in sporadic cancer; somatic mutation; Loss FT of kinase activity)" FT /evidence="ECO:0000269|PubMed:12805220, FT ECO:0000269|PubMed:19892943" FT /id="VAR_065637" FT VARIANT 177 FT /note="I -> N (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39; dbSNP:rs1057520041)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065638" FT VARIANT 181 FT /note="N -> E (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39; requires 2 nucleotide substitutions; FT dbSNP:rs1568707668)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065639" FT VARIANT 194 FT /note="D -> N (in PJS; dbSNP:rs121913315)" FT /evidence="ECO:0000269|PubMed:10408777" FT /id="VAR_007921" FT VARIANT 194 FT /note="D -> V (in lung cancer; somatic mutation; FT dbSNP:rs121913316)" FT /evidence="ECO:0000269|PubMed:10079245" FT /id="VAR_065640" FT VARIANT 194 FT /note="D -> Y (in melanoma; sporadic malignant; somatic FT mutation; dbSNP:rs121913315)" FT /evidence="ECO:0000269|PubMed:10208439" FT /id="VAR_033141" FT VARIANT 199 FT /note="E -> K (in colorectal cancer; somatic mutation; FT impaired kinase activity; dbSNP:rs121913317)" FT /evidence="ECO:0000269|PubMed:9731485" FT /id="VAR_065641" FT VARIANT 199 FT /note="E -> Q (in sporadic cancer; somatic mutation; does FT not affect kinase activity)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065642" FT VARIANT 205 FT /note="A -> T (in sporadic cancer; somatic mutation; no FT effect heterotrimeric complex assembly with STRADA and FT CAB39; dbSNP:rs730881981)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065643" FT VARIANT 208 FT /note="D -> N (in colorectal cancer; somatic mutation; no FT effect heterotrimeric complex assembly with STRADA and FT CAB39; dbSNP:rs1555738372)" FT /evidence="ECO:0000269|PubMed:9731485" FT /id="VAR_065644" FT VARIANT 215 FT /note="G -> D (in colorectal cancer; somatic mutation; FT dbSNP:rs1057520038)" FT /evidence="ECO:0000269|PubMed:9731485" FT /id="VAR_065645" FT VARIANT 216 FT /note="S -> F (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39; dbSNP:rs1057520017)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065646" FT VARIANT 223 FT /note="E -> V (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065647" FT VARIANT 230 FT /note="T -> P (in sporadic cancer; somatic mutation; no FT effect heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065648" FT VARIANT 231 FT /note="F -> L (in cervical cancer; somatic mutation; FT dbSNP:rs929783669)" FT /evidence="ECO:0000269|PubMed:12533684" FT /id="VAR_065649" FT VARIANT 232 FT /note="S -> P (in sporadic cancer; somatic mutation; no FT effect heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065650" FT VARIANT 239 FT /note="W -> C (in PJS; late onset suggests reduced FT penetrance; dbSNP:rs137853082)" FT /evidence="ECO:0000269|PubMed:12372054" FT /id="VAR_033142" FT VARIANT 245 FT /note="L -> R (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065651" FT VARIANT 247 FT /note="Missing (in PJS)" FT /evidence="ECO:0000269|PubMed:9760200" FT /id="VAR_006203" FT VARIANT 250 FT /note="T -> P (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065652" FT VARIANT 272 FT /note="Y -> H (in sporadic cancer; somatic mutation; no FT effect on kinase activity nor in heterotrimeric complex FT assembly with STRADA and CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065653" FT VARIANT 277 FT /note="D -> Y (in sporadic cancer; somatic mutation; no FT effect on kinase activity nor in heterotrimeric complex FT assembly with STRADA and CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065654" FT VARIANT 281 FT /note="P -> L (in ovarian carcinoma; somatic mutation; FT dbSNP:rs121913322)" FT /evidence="ECO:0000269|PubMed:10429654" FT /id="VAR_065655" FT VARIANT 285 FT /note="L -> Q (in sporadic cancer; somatic mutation; FT impairs heterotrimeric complex assembly with STRADA and FT CAB39)" FT /evidence="ECO:0000269|PubMed:19892943" FT /id="VAR_065656" FT VARIANT 297 FT /note="R -> K (in PJS; dbSNP:rs1568710381)" FT /evidence="ECO:0000269|PubMed:10408777" FT /id="VAR_007922" FT VARIANT 303..306 FT /note="IRQH -> N (in PJS)" FT /id="VAR_033143" FT VARIANT 308 FT /note="W -> C (in PJS; abolishes kinase activity, leading FT to loss of autophosphorylation; dbSNP:rs1057520042)" FT /evidence="ECO:0000269|PubMed:9837816" FT /id="VAR_071059" FT VARIANT 314 FT /note="P -> H (in colorectal cancer; no effect FT heterotrimeric complex assembly with STRADA and CAB39)" FT /evidence="ECO:0000269|PubMed:9809980" FT /id="VAR_065657" FT VARIANT 315 FT /note="P -> S (in PJS; uncertain significance; no effect FT heterotrimeric complex assembly with STRADA and CAB39; FT dbSNP:rs786202431)" FT /evidence="ECO:0000269|PubMed:12372054, FT ECO:0000269|PubMed:19892943" FT /id="VAR_033144" FT VARIANT 324 FT /note="P -> L (in gastric carcinoma; no effect FT heterotrimeric complex assembly with STRADA and CAB39; FT dbSNP:rs367807476)" FT /evidence="ECO:0000269|PubMed:9683800" FT /id="VAR_065658" FT VARIANT 354 FT /note="F -> L (in colorectal cancer; somatic mutation; FT dbSNP:rs59912467)" FT /evidence="ECO:0000269|PubMed:9731485" FT /id="VAR_065659" FT VARIANT 367 FT /note="T -> M (in colorectal cancer; somatic mutation; FT dbSNP:rs587782835)" FT /evidence="ECO:0000269|PubMed:9731485" FT /id="VAR_065660" FT MUTAGEN 44 FT /note="K->R: No effect on kinase activity." FT /evidence="ECO:0000269|PubMed:18687677" FT MUTAGEN 48 FT /note="K->Q: No effect on basal nucleocytoplasmic FT localization, but fails to translocate to the cytoplasm FT when coexpressed with SIRT1." FT /evidence="ECO:0000269|PubMed:18687677" FT MUTAGEN 48 FT /note="K->R: Enhanced phosphorylation at Thr-336 and FT Ser-428, enhanced cytoplasmic localization and increased FT kinase activity." FT /evidence="ECO:0000269|PubMed:18687677" FT MUTAGEN 74 FT /note="R->A: Impaired formation of a heterotrimeric complex FT with STRADA and CAB39; when associated with A-204." FT /evidence="ECO:0000269|PubMed:19892943" FT MUTAGEN 78 FT /note="K->I: Loss of kinase activity, leading to greatly FT reduced autophosphorylation." FT /evidence="ECO:0000269|PubMed:11430832, FT ECO:0000269|PubMed:9837816" FT MUTAGEN 78 FT /note="K->M: Loss of kinase activity, leading to reduced FT autophosphorylation and acting as a dominant-negative FT mutant." FT /evidence="ECO:0000269|PubMed:11430832, FT ECO:0000269|PubMed:9837816" FT MUTAGEN 96 FT /note="K->R: No effect on kinase activity." FT /evidence="ECO:0000269|PubMed:18687677" FT MUTAGEN 97 FT /note="K->R: No effect on kinase activity." FT /evidence="ECO:0000269|PubMed:18687677" FT MUTAGEN 189 FT /note="T->A: Reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:11430832" FT MUTAGEN 194 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:14517248, FT ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:19892943" FT MUTAGEN 204 FT /note="F->A: No effect. Impaired formation of a FT heterotrimeric complex with STRADA and CAB39; when FT associated with A-74." FT /evidence="ECO:0000269|PubMed:19892943" FT MUTAGEN 428 FT /note="S->A,E: No effect on kinase activity." FT /evidence="ECO:0000269|PubMed:18854309" FT STRAND 54..57 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 62..68 FT /evidence="ECO:0007829|PDB:2WTK" FT TURN 69..71 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 74..80 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 82..87 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 91..102 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 113..118 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 125..130 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 150..169 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 179..181 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 222..225 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 234..250 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 260..269 FT /evidence="ECO:0007829|PDB:2WTK" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 280..289 FT /evidence="ECO:0007829|PDB:2WTK" FT TURN 294..296 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 300..305 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 307..310 FT /evidence="ECO:0007829|PDB:2WTK" FT HELIX 334..336 FT /evidence="ECO:0007829|PDB:4ZDR" FT HELIX 339..341 FT /evidence="ECO:0007829|PDB:2WTK" FT MOD_RES Q15831-2:399 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23612973" SQ SEQUENCE 433 AA; 48636 MW; 6DF4C37AB7A89569 CRC64; MEVVDPQQLG MFTEGELMSV GMDTFIHRID STEVIYQPRR KRAKLIGKYL MGDLLGEGSY GKVKEVLDSE TLCRRAVKIL KKKKLRRIPN GEANVKKEIQ LLRRLRHKNV IQLVDVLYNE EKQKMYMVME YCVCGMQEML DSVPEKRFPV CQAHGYFCQL IDGLEYLHSQ GIVHKDIKPG NLLLTTGGTL KISDLGVAEA LHPFAADDTC RTSQGSPAFQ PPEIANGLDT FSGFKVDIWS AGVTLYNITT GLYPFEGDNI YKLFENIGKG SYAIPGDCGP PLSDLLKGML EYEPAKRFSI RQIRQHSWFR KKHPPAEAPV PIPPSPDTKD RWRSMTVVPY LEDLHGADED EDLFDIEDDI IYTQDFTVPG QVPEEEASHN GQRRGLPKAV CMNGTEAAQL STKSRAEGRA PNPARKACSA SSKIRRLSAC KQQ //