STK11_HUMAN
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 03-AUG-2022, entry version 228.
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-ASN--MET-164; 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=14; IntAct=EBI-306838, EBI-306905;
CC Q15831; Q16543: CDC37; NbExp=4; IntAct=EBI-306838, EBI-295634;
CC Q15831; Q9BT78: COPS4; NbExp=3; IntAct=EBI-306838, EBI-742413;
CC Q15831; Q13451: FKBP5; NbExp=6; 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=14; IntAct=EBI-306838, EBI-1109114;
CC Q15831; Q7RTN6-1: STRADA; NbExp=3; IntAct=EBI-306838, EBI-15787241;
CC Q15831; Q9C0K7: STRADB; NbExp=8; 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="http://atlasgeneticsoncology.org/Genes/STK11ID292.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=PJS entry;
CC URL="https://en.wikipedia.org/wiki/PJS";
CC ---------------------------------------------------------------------------
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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; 246.
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; 130.
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 EPD; Q15831; -.
DR jPOST; Q15831; -.
DR MassIVE; Q15831; -.
DR MaxQB; Q15831; -.
DR PaxDb; Q15831; -.
DR PeptideAtlas; Q15831; -.
DR PRIDE; Q15831; -.
DR ProteomicsDB; 60780; -. [Q15831-1]
DR ProteomicsDB; 60781; -. [Q15831-2]
DR Antibodypedia; 2048; 1373 antibodies from 44 providers.
DR DNASU; 6794; -.
DR Ensembl; ENST00000326873.12; ENSP00000324856.6; ENSG00000118046.17. [Q15831-1]
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 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; GMFAESE; -.
DR OrthoDB; 1246375at2759; -.
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; 142 hits in 1128 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 154 other tissues.
DR ExpressionAtlas; Q15831; baseline and differential.
DR Genevisible; Q15831; HS.
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:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0071493; P:cellular response to UV-B; IDA:UniProtKB.
DR GO; GO:0097484; P:dendrite extension; IEA:Ensembl.
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 protein kinase B signaling; 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 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 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 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 /id="VAR_007920"
FT VARIANT 163
FT /note="G -> D (in TGCT; a tumor with seminoma and teratoma
FT components; associated with severely impaired but
FT detectable kinase activity; somatic mutation; impairs
FT heterotrimeric complex assembly with STRADA and CAB39;
FT predominantly nuclear 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; pathogenicity uncertain; 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 Ser-
FT 428, enhanced cytoplasmic localization and increased kinase
FT 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
