STK11_MOUSE
ID STK11_MOUSE Reviewed; 436 AA.
AC Q9WTK7; A0A2L1DGD8; B3VBP0; Q3TAE0;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein kinase STK11 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q15831};
DE AltName: Full=Liver kinase B1 homolog;
DE Short=LKB1;
DE Short=mLKB1;
DE Flags: Precursor;
GN Name=Stk11 {ECO:0000312|MGI:MGI:1341870};
GN Synonyms=Lkb1 {ECO:0000312|EMBL:AAD55368.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD22100.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RX PubMed=10381580; DOI=10.1016/s0925-4773(99)00050-7;
RA Luukko K., Ylikorkala A., Tiainen M., Makela T.P.;
RT "Expression of LKB1 and PTEN tumor suppressor genes during mouse embryonic
RT development.";
RL Mech. Dev. 83:187-190(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD55368.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND SUBCELLULAR
RP LOCATION.
RC STRAIN=129 {ECO:0000312|EMBL:AAD55368.1};
RX PubMed=10400995; DOI=10.1093/hmg/8.8.1479;
RA Smith D.P., Spicer J., Smith A., Swift S., Ashworth A.;
RT "The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein
RT kinase.";
RL Hum. Mol. Genet. 8:1479-1485(1999).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAF21370.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PALMITOYLATION AT CYS-422, PHOSPHORYLATION AT SER-431,
RP ISOPRENYLATION AT CYS-433, AND MUTAGENESIS OF SER-431 AND CYS-433.
RX PubMed=10642527; DOI=10.1042/bj3450673;
RA Collins S.P., Reoma J.L., Gamm D.M., Uhler M.D.;
RT "LKB1, a novel serine/threonine protein kinase and potential tumour
RT suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and
RT prenylated in vivo.";
RL Biochem. J. 345:673-680(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:BAA76749.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=Swiss Webster / NIH {ECO:0000312|EMBL:BAA76749.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAA76749.1};
RX PubMed=12060709; DOI=10.1073/pnas.122254599;
RA Jishage K., Nezu J., Kawase Y., Iwata T., Watanabe M., Miyoshi A., Ose A.,
RA Habu K., Kake T., Kamada N., Ueda O., Kinoshita M., Jenne D.E., Shimane M.,
RA Suzuki H.;
RT "Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in
RT embryogenesis and polyposis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8903-8908(2002).
RN [5] {ECO:0000312|EMBL:AVC68843.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=29777910; DOI=10.1016/j.gene.2018.05.053;
RA Ishqi H.M., Sarwar T., Husain M.A., Rehman S.U., Tabish M.;
RT "Differentially expressed novel alternatively spliced transcript variant of
RT tumor suppressor Stk11 gene in mouse.";
RL Gene 668:146-154(2018).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Ido Y., Lan F.;
RL Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305, ECO:0000312|EMBL:BAE42977.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=NOD {ECO:0000312|EMBL:BAE42977.1};
RC TISSUE=Spleen {ECO:0000312|EMBL:BAE42977.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [8] {ECO:0000305, ECO:0000312|EMBL:AAH52379.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH52379.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH52379.1};
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 [9]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-431, ISOPRENYLATION AT
RP CYS-433, AND MUTAGENESIS OF SER-431 AND CYS-433.
RX PubMed=11297520; DOI=10.1074/jbc.m009953200;
RA Sapkota G.P., Kieloch A., Lizcano J.M., Lain S., Arthur J.S.,
RA Williams M.R., Morrice N., Deak M., Alessi D.R.;
RT "Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer
RT syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein
RT kinase, but not its farnesylation at Cys(433), is essential for LKB1 to
RT suppress cell vrowth.";
RL J. Biol. Chem. 276:19469-19482(2001).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=11509733; DOI=10.1126/science.1062074;
RA Ylikorkala A., Rossi D.J., Korsisaari N., Luukko K., Alitalo K.,
RA Henkemeyer M., Makela T.P.;
RT "Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice.";
RL Science 293:1323-1326(2001).
RN [11]
RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-31;
RP SER-325; THR-336 AND THR-366, ISOPRENYLATION AT CYS-433, METHYLATION AT
RP CYS-433, AND MUTAGENESIS OF SER-31; ASP-194; SER-325; THR-336; THR-366 AND
RP CYS-433.
RX PubMed=11853558; DOI=10.1042/0264-6021:3620481;
RA Sapkota G.P., Boudeau J., Deak M., Kieloch A., Morrice N., Alessi D.R.;
RT "Identification and characterization of four novel phosphorylation sites
RT (Ser31, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase
RT mutated in Peutz-Jeghers cancer syndrome.";
RL Biochem. J. 362:481-490(2002).
RN [12]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-366, AND MUTAGENESIS OF
RP THR-366.
RX PubMed=12234250; DOI=10.1042/bj20021284;
RA Sapkota G.P., Deak M., Kieloch A., Morrice N., Goodarzi A.A., Smythe C.,
RA Shiloh Y., Lees-Miller S.P., Alessi D.R.;
RT "Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-
RT mediated phosphorylation of LKB1/STK11 at Thr-366.";
RL Biochem. J. 368:507-516(2002).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=11956081;
RA Miyoshi H., Nakau M., Ishikawa T.O., Seldin M.F., Oshima M., Taketo M.M.;
RT "Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout
RT mice.";
RL Cancer Res. 62:2261-2266(2002).
RN [14]
RP DISRUPTION PHENOTYPE.
RX PubMed=12226664; DOI=10.1038/nature01045;
RA Bardeesy N., Sinha M., Hezel A.F., Signoretti S., Hathaway N.A.,
RA Sharpless N.E., Loda M., Carrasco D.R., DePinho R.A.;
RT "Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but
RT resistance to transformation.";
RL Nature 419:162-167(2002).
RN [15]
RP DISRUPTION PHENOTYPE.
RX PubMed=12218179; DOI=10.1073/pnas.192301399;
RA Rossi D.J., Ylikorkala A., Korsisaari N., Salovaara R., Luukko K.,
RA Launonen V., Henkemeyer M., Ristimaki A., Aaltonen L.A., Makela T.P.;
RT "Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers
RT polyposis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12327-12332(2002).
RN [16]
RP DISRUPTION PHENOTYPE.
RX PubMed=15480979; DOI=10.1053/j.gastro.2004.07.059;
RA Udd L., Katajisto P., Rossi D.J., Lepisto A., Lahesmaa A.M., Ylikorkala A.,
RA Jarvinen H.J., Ristimaki A.P., Makela T.P.;
RT "Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-
RT 2.";
RL Gastroenterology 127:1030-1037(2004).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16308421; DOI=10.1126/science.1120781;
RA Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N., Depinho R.A.,
RA Montminy M., Cantley L.C.;
RT "The kinase LKB1 mediates glucose homeostasis in liver and therapeutic
RT effects of metformin.";
RL Science 310:1642-1646(2005).
RN [19]
RP FUNCTION, PHOSPHORYLATION AT SER-431, MUTAGENESIS OF SER-431, SUBCELLULAR
RP LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH STRADA.
RX PubMed=17482548; DOI=10.1016/j.cell.2007.03.025;
RA Barnes A.P., Lilley B.N., Pan Y.A., Plummer L.J., Powell A.W., Raines A.N.,
RA Sanes J.R., Polleux F.;
RT "LKB1 and SAD kinases define a pathway required for the polarization of
RT cortical neurons.";
RL Cell 129:549-563(2007).
RN [20]
RP FUNCTION, PHOSPHORYLATION AT SER-431, AND MUTAGENESIS OF SER-431.
RX PubMed=17482549; DOI=10.1016/j.cell.2007.04.012;
RA Shelly M., Cancedda L., Heilshorn S., Sumbre G., Poo M.M.;
RT "LKB1/STRAD promotes axon initiation during neuronal polarization.";
RL Cell 129:565-577(2007).
RN [21]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION (ISOFORM 2), TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18774945; DOI=10.1042/bj20081447;
RA Towler M.C., Fogarty S., Hawley S.A., Pan D.A., Martin D.M., Morrice N.A.,
RA McCarthy A., Galardo M.N., Meroni S.B., Cigorraga S.B., Ashworth A.,
RA Sakamoto K., Hardie D.G.;
RT "A novel short splice variant of the tumour suppressor LKB1 is required for
RT spermiogenesis.";
RL Biochem. J. 416:1-14(2008).
RN [22]
RP ACETYLATION.
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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [24]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [26]
RP FUNCTION, PHOSPHORYLATION AT THR-366, AND MUTAGENESIS OF THR-366.
RX PubMed=20864035; DOI=10.1016/j.molcel.2010.08.019;
RA Sherman M.H., Kuraishy A.I., Deshpande C., Hong J.S., Cacalano N.A.,
RA Gatti R.A., Manis J.P., Damore M.A., Pellegrini M., Teitell M.A.;
RT "AID-induced genotoxic stress promotes B cell differentiation in the
RT germinal center via ATM and LKB1 signaling.";
RL Mol. Cell 39:873-885(2010).
RN [27]
RP FUNCTION, INTERACTION WITH CDKN1A, PHOSPHORYLATION AT THR-366, AND
RP MUTAGENESIS OF THR-366.
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).
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:16308421,
CC ECO:0000269|PubMed:17482548, ECO:0000269|PubMed:17482549,
CC ECO:0000269|PubMed:20864035, ECO:0000269|PubMed:25329316}.
CC -!- FUNCTION: [Isoform 2]: Has a role in spermiogenesis.
CC {ECO:0000269|PubMed:18774945}.
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:0000250|UniProtKB:Q15831};
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:0000250|UniProtKB:Q15831};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q15831};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q15831};
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 (By similarity). {ECO:0000250}.
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 (By similarity). Interacts with
CC NISCH; this interaction may increase STK11 activity (By similarity).
CC Interacts with PTEN, leading to PTEN phosphorylation (By similarity).
CC Interacts with SIRT1; the interaction deacetylates STK11 (By
CC similarity). Interacts with CDKN1A. {ECO:0000250|UniProtKB:Q15831,
CC ECO:0000269|PubMed:17482548, ECO:0000269|PubMed:25329316}.
CC -!- INTERACTION:
CC Q9WTK7; Q9CSB4: Pard3b; NbExp=2; IntAct=EBI-8627450, EBI-16107395;
CC Q9WTK7; P54646: PRKAA2; Xeno; NbExp=2; IntAct=EBI-8627450, EBI-1383852;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Membrane. Mitochondrion
CC {ECO:0000250}. Note=Translocates to mitochondrion during apoptosis (By
CC similarity). A small fraction localizes at membranes. Relocates to the
CC cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25
CC (CAB39/MO25alpha or CAB39L/MO25beta). PTEN promotes cytoplasmic
CC localization (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Note=Relocates to the cytoplasm when bound to STRAD
CC (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:10381580, ECO:0000269|PubMed:10400995,
CC ECO:0000269|PubMed:10642527, ECO:0000269|PubMed:12060709,
CC ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16141072};
CC Synonyms=LKB1(L), STK11C {ECO:0000303|PubMed:29777910};
CC IsoId=Q9WTK7-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072}; Synonyms=LKB1(S);
CC IsoId=Q9WTK7-2; Sequence=VSP_052222, VSP_052223;
CC Name=3; Synonyms=STK11N {ECO:0000303|PubMed:29777910};
CC IsoId=Q9WTK7-3; Sequence=VSP_060609, VSP_060610;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Widely expressed.
CC {ECO:0000269|PubMed:10642527, ECO:0000269|PubMed:18774945,
CC ECO:0000269|PubMed:18854309}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Predominantly expressed in testis (at
CC protein level). {ECO:0000269|PubMed:18774945}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in adult brain and liver and
CC absent from tissues derived from postnatal day 7.
CC {ECO:0000269|PubMed:29777910}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed 7-11 dpc. Present in
CC nucleated embryonic blood cells from 9 dpc. Restricted to
CC gastrointestinal tract, testis and lung from days 15-19 dpc.
CC {ECO:0000269|PubMed:10381580, ECO:0000269|PubMed:12060709}.
CC -!- PTM: Phosphorylated by ATM at Thr-366 following ionizing radiation
CC (IR). Phosphorylation at Ser-431 by RPS6KA1 and/or some PKA is required
CC to inhibit cell growth. Phosphorylation at Ser-431 is also required
CC during neuronal polarization to mediate phosphorylation of BRSK1 and
CC BRSK2. Phosphorylation by PKC/PRKCZ at Ser-399 in isoform 2 promotes
CC metformin (or peroxynitrite)-induced nuclear export of STK11 and
CC activation of AMPK. UV radiation-induced phosphorylation at Thr-366
CC mediates CDKN1A degradation. {ECO:0000269|PubMed:10642527,
CC ECO:0000269|PubMed:11297520, ECO:0000269|PubMed:11853558,
CC ECO:0000269|PubMed:12234250, ECO:0000269|PubMed:17482548,
CC ECO:0000269|PubMed:17482549, ECO:0000269|PubMed:20864035,
CC ECO:0000269|PubMed:25329316}.
CC -!- PTM: Acetylated. Deacetylation at Lys-48 enhances cytoplasmic
CC localization and kinase activity in vitro.
CC {ECO:0000269|PubMed:18687677}.
CC -!- DISRUPTION PHENOTYPE: Mice die in utero 8.5 to 9.5 dpc due to severe
CC defects in their vasculature: embryos show neural tube defects,
CC mesenchymal cell death, and vascular abnormalities. Extraembryonic
CC development is also severely affected; the mutant placentas exhibit
CC defective labyrinth layer development and the fetal vessels fail to
CC invade the placenta. Male mice specifically lacking isoform 2 are
CC sterile (PubMed:18774945). A specifically deletion in liver results in
CC hyperglycemia with increased gluconeogenic and lipogenic gene
CC expression due to loss of AMPK phosphorylation and subsequent
CC dephosphorylation of CRTC2/TORC2 (PubMed:16308421). Use of a
CC conditional allele, leads to defects in defects in axon formation with
CC a thinner cortical wall and larger lateral ventricles in the brain
CC cortex (PubMed:17482548). Heterozygous mice develop multiple gastric
CC adenomatous polyps, with polyps remarkably similar to hamartomas of PJS
CC patients both macroscopically and histologically. Polyps in the
CC heterozygous mice are detected at 5 months, and cause premature
CC lethality progressively from 8 months onwards. Polyps are most
CC frequently observed in the stomach where they typically concentrate
CC close to the pylorus. Polyps in the small and large intestine are
CC significantly less frequent. The histology of the polyps in the
CC heterozygous mice is remarkably similar to PJS polyps including the
CC relative contribution of well-differentiated epithelium, and a
CC prominent smooth muscle component. Ptgs2/Cox2 is highly up-regulated in
CC heterozygous mice polyps concomitantly with activation of the
CC extracellular signal-regulated kinases Mapk1/Erk2 and Mapk3/Erk1:
CC treatment with celecoxib Ptgs2/Cox2 inhibitor significantly reduces the
CC total polyp burden. {ECO:0000269|PubMed:11509733,
CC ECO:0000269|PubMed:11956081, ECO:0000269|PubMed:12060709,
CC ECO:0000269|PubMed:12218179, ECO:0000269|PubMed:12226664,
CC ECO:0000269|PubMed:15480979, ECO:0000269|PubMed:16308421,
CC ECO:0000269|PubMed:17482548, ECO:0000269|PubMed:18774945}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. LKB1 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; AF129870; AAD22100.1; -; mRNA.
DR EMBL; AF145287; AAD31044.1; -; mRNA.
DR EMBL; EU730638; ACE73833.1; -; mRNA.
DR EMBL; AF145296; AAD55368.1; -; Genomic_DNA.
DR EMBL; AF145288; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145289; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145290; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145291; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145292; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145293; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145294; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF145295; AAD55368.1; JOINED; Genomic_DNA.
DR EMBL; AF151711; AAF21370.1; -; mRNA.
DR EMBL; AB015801; BAA76749.1; -; mRNA.
DR EMBL; KY779728; AVC68843.1; -; mRNA.
DR EMBL; AK171909; BAE42728.1; -; mRNA.
DR EMBL; AK172528; BAE43050.1; -; mRNA.
DR EMBL; AK172385; BAE42977.1; -; mRNA.
DR EMBL; BC052379; AAH52379.1; -; mRNA.
DR CCDS; CCDS35974.1; -. [Q9WTK7-1]
DR CCDS; CCDS78854.1; -. [Q9WTK7-2]
DR RefSeq; NP_001288782.1; NM_001301853.1. [Q9WTK7-2]
DR RefSeq; NP_001288783.1; NM_001301854.1.
DR RefSeq; NP_035622.1; NM_011492.4. [Q9WTK7-1]
DR AlphaFoldDB; Q9WTK7; -.
DR SMR; Q9WTK7; -.
DR BioGRID; 203541; 12.
DR CORUM; Q9WTK7; -.
DR DIP; DIP-60722N; -.
DR ELM; Q9WTK7; -.
DR IntAct; Q9WTK7; 7.
DR MINT; Q9WTK7; -.
DR STRING; 10090.ENSMUSP00000003152; -.
DR ChEMBL; CHEMBL3734644; -.
DR iPTMnet; Q9WTK7; -.
DR PhosphoSitePlus; Q9WTK7; -.
DR EPD; Q9WTK7; -.
DR jPOST; Q9WTK7; -.
DR MaxQB; Q9WTK7; -.
DR PaxDb; Q9WTK7; -.
DR PeptideAtlas; Q9WTK7; -.
DR PRIDE; Q9WTK7; -.
DR ProteomicsDB; 254588; -. [Q9WTK7-1]
DR ProteomicsDB; 254589; -. [Q9WTK7-2]
DR Antibodypedia; 2048; 1373 antibodies from 44 providers.
DR DNASU; 20869; -.
DR Ensembl; ENSMUST00000003152; ENSMUSP00000003152; ENSMUSG00000003068. [Q9WTK7-1]
DR Ensembl; ENSMUST00000144883; ENSMUSP00000114195; ENSMUSG00000003068. [Q9WTK7-2]
DR GeneID; 20869; -.
DR KEGG; mmu:20869; -.
DR UCSC; uc007gbt.2; mouse. [Q9WTK7-1]
DR CTD; 6794; -.
DR MGI; MGI:1341870; Stk11.
DR VEuPathDB; HostDB:ENSMUSG00000003068; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000158050; -.
DR HOGENOM; CLU_000288_1_2_1; -.
DR InParanoid; Q9WTK7; -.
DR OMA; GMFAESE; -.
DR PhylomeDB; Q9WTK7; -.
DR TreeFam; TF105322; -.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR BioGRID-ORCS; 20869; 20 hits in 81 CRISPR screens.
DR PRO; PR:Q9WTK7; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9WTK7; protein.
DR Bgee; ENSMUSG00000003068; Expressed in ileal epithelium and 269 other tissues.
DR ExpressionAtlas; Q9WTK7; baseline and differential.
DR Genevisible; Q9WTK7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0140535; C:intracellular protein-containing complex; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; ISO:MGI.
DR GO; GO:0030018; C:Z disc; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0030275; F:LRR domain binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISS: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; ISO:MGI.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:MGI.
DR GO; GO:0043276; P:anoikis; ISO:MGI.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB.
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; IMP:MGI.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:UniProtKB.
DR GO; GO:0070314; P:G1 to G0 transition; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0051645; P:Golgi localization; IMP:MGI.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA: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; IMP:YuBioLab.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IGI:MGI.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:MGI.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IMP:MGI.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:MGI.
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; IDA:UniProtKB.
DR GO; GO:0033993; P:response to lipid; ISO:MGI.
DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0001894; P:tissue homeostasis; IMP:MGI.
DR GO; GO:0001944; P:vasculature development; IMP:UniProtKB.
DR CDD; cd14119; STKc_LKB1; 1.
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 Acetylation; Alternative splicing; Apoptosis; ATP-binding; Autophagy;
KW Cell cycle; Cytoplasm; Differentiation; DNA damage; Kinase; Lipoprotein;
KW Magnesium; Manganese; Membrane; Metal-binding; Methylation; Mitochondrion;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Prenylation;
KW Reference proteome; Serine/threonine-protein kinase; Spermatogenesis;
KW Transferase; Tumor suppressor.
FT CHAIN 1..433
FT /note="Serine/threonine-protein kinase STK11"
FT /id="PRO_0000260032"
FT PROPEP 434..436
FT /note="Removed in mature form"
FT /id="PRO_0000422301"
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:0000250"
FT REGION 397..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 55..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT 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:0000269|PubMed:11853558,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 44
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 48
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 96
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 189
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 296
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 311
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11853558"
FT MOD_RES 336
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11853558"
FT MOD_RES 366
FT /note="Phosphothreonine; by ATM and autocatalysis"
FT /evidence="ECO:0000269|PubMed:11853558,
FT ECO:0000269|PubMed:12234250, ECO:0000269|PubMed:20864035,
FT ECO:0000269|PubMed:25329316"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 420
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 426
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT MOD_RES 431
FT /note="Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and
FT RPS6KA1"
FT /evidence="ECO:0000269|PubMed:10642527,
FT ECO:0000269|PubMed:11297520, ECO:0000269|PubMed:17482548,
FT ECO:0000269|PubMed:17482549"
FT MOD_RES 433
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:11853558"
FT MOD_RES 434
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15831"
FT LIPID 422
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:10642527"
FT LIPID 433
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:10642527,
FT ECO:0000269|PubMed:11297520, ECO:0000269|PubMed:11853558"
FT VAR_SEQ 98..232
FT /note="EIQLLRRLRHRNVIQLVDVLYNEEKQKMYMVMEYCVCGMQEMLDSVPEKRFP
FT VCQAHGYFRQLIDGLEYLHSQGIVHKDIKPGNLLLTTNGTLKISDLGVAEALHPFAVDD
FT TCRTSQGSPAFQPPEIANGLDTFS -> PCTLSLWMTPAGQARAPRPSSLLRLPMDWTP
FT FQVSRWTSGQLGSHFTTSPRACTHLRGTISTSSLRTLGEETSPSLVTAAHHSLTYSEGC
FT WSMSRPRGSPSDRLGSTAGSGRNTLWLRRSYLSHQAQTLRTAGAV (in isoform
FT 3)"
FT /evidence="ECO:0000269|PubMed:29777910"
FT /id="VSP_060609"
FT VAR_SEQ 233..436
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000269|PubMed:29777910"
FT /id="VSP_060610"
FT VAR_SEQ 374..415
FT /note="QVLEEEVGQNGQSHSLPKAVCVNGTEPQLSSKVKPEGRPGTA -> VEEAAE
FT AGLSEDACDTCMWKSQGAGLPGEEPEEGFGALV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.6"
FT /id="VSP_052222"
FT VAR_SEQ 416..436
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.6"
FT /id="VSP_052223"
FT MUTAGEN 31
FT /note="S->A: No change in kinase activity; when associated
FT with A-325; A-336 and A-366."
FT /evidence="ECO:0000269|PubMed:11853558"
FT MUTAGEN 78
FT /note="K->I: Loss of kinase activity."
FT MUTAGEN 194
FT /note="D->A: Loss of kinase activity and descreased
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11853558"
FT MUTAGEN 325
FT /note="S->A: No change in kinase activity; when associated
FT with A-31; A-336 and A-366."
FT /evidence="ECO:0000269|PubMed:11853558"
FT MUTAGEN 336
FT /note="T->A: Abolishes ability to suppress cell growth.
FT Decreased phosphorylation; when associated with A-366. No
FT change in kinase activity; when associated with A-31; A-325
FT and A-366."
FT /evidence="ECO:0000269|PubMed:11853558"
FT MUTAGEN 366
FT /note="T->A: Diminished interaction with CDKN1A and
FT impaired ability to repair UV-induced DNA damage by
FT affecting CDKN1A UV-induced degradation. Decreased
FT phosphorylation; when associated with A-336. No change in
FT kinase activity; when associated with A-31; A-325 and A-
FT 336."
FT /evidence="ECO:0000269|PubMed:11853558,
FT ECO:0000269|PubMed:12234250, ECO:0000269|PubMed:20864035,
FT ECO:0000269|PubMed:25329316"
FT MUTAGEN 431
FT /note="S->A: Does not prevent S-farnesylation. Defects in
FT neuron polarization."
FT /evidence="ECO:0000269|PubMed:10642527,
FT ECO:0000269|PubMed:11297520, ECO:0000269|PubMed:17482548,
FT ECO:0000269|PubMed:17482549"
FT MUTAGEN 433
FT /note="C->A: Does not affect nuclear localization. Does not
FT prevent phosphorylation at S-431."
FT /evidence="ECO:0000269|PubMed:10642527,
FT ECO:0000269|PubMed:11297520, ECO:0000269|PubMed:11853558"
FT CONFLICT 95
FT /note="V -> L (in Ref. 2; BAE42728)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 436 AA; 49267 MW; CCD9BCF94CF5CC9C CRC64;
MDVADPEPLG LFSEGELMSV GMDTFIHRID STEVIYQPRR KRAKLIGKYL MGDLLGEGSY
GKVKEVLDSE TLCRRAVKIL KKKKLRRIPN GEANVKKEIQ LLRRLRHRNV IQLVDVLYNE
EKQKMYMVME YCVCGMQEML DSVPEKRFPV CQAHGYFRQL IDGLEYLHSQ GIVHKDIKPG
NLLLTTNGTL KISDLGVAEA LHPFAVDDTC RTSQGSPAFQ PPEIANGLDT FSGFKVDIWS
AGVTLYNITT GLYPFEGDNI YKLFENIGRG DFTIPCDCGP PLSDLLRGML EYEPAKRFSI
RQIRQHSWFR KKHPLAEALV PIPPSPDTKD RWRSMTVVPY LEDLHGRAEE EEEEDLFDIE
DGIIYTQDFT VPGQVLEEEV GQNGQSHSLP KAVCVNGTEP QLSSKVKPEG RPGTANPARK
VCSSNKIRRL SACKQQ
