ID   BRSK2_MOUSE             Reviewed;         735 AA.
AC   Q69Z98; Q699J3; Q699J4; Q6DMN7; Q6PHM0;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 157.
DE   RecName: Full=Serine/threonine-protein kinase BRSK2;
DE            EC=2.7.11.1;
DE            EC=2.7.11.26;
DE   AltName: Full=Brain-specific serine/threonine-protein kinase 2;
DE            Short=BR serine/threonine-protein kinase 2;
DE   AltName: Full=Serine/threonine-protein kinase SAD-A;
GN   Name=Brsk2; Synonyms=Kiaa4256, Sada;
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]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), FUNCTION, MUTAGENESIS OF
RP   LYS-49, AND DISRUPTION PHENOTYPE.
RX   PubMed=15705853; DOI=10.1126/science.1107403;
RA   Kishi M., Pan Y.A., Crump J.G., Sanes J.R.;
RT   "Mammalian SAD kinases are required for neuronal polarization.";
RL   Science 307:929-932(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA   Tang W.W., Shan Y.X.;
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-735 (ISOFORM 1).
RC   TISSUE=Fetal brain;
RX   PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA   Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT   The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 11:205-218(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 131-653 (ISOFORM 4).
RC   STRAIN=C57BL/6J; TISSUE=Brain;
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   [6]
RP   FUNCTION, PHOSPHORYLATION AT THR-175, AND MUTAGENESIS OF THR-175.
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383; SER-394; SER-413;
RP   SER-424; SER-428; SER-456; THR-460; THR-464; THR-510; SER-513; SER-514 AND
RP   SER-521, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Pancreas, 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   [8]
RP   FUNCTION.
RX   PubMed=20026642; DOI=10.1242/jcs.058230;
RA   Muller M., Lutter D., Puschel A.W.;
RT   "Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-
RT   deficient neurons disrupts neuronal polarity.";
RL   J. Cell Sci. 123:286-294(2010).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PAK1.
RX   PubMed=22669945; DOI=10.1074/jbc.m112.378372;
RA   Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W.,
RA   Han X., Shi Y.;
RT   "Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated
RT   insulin secretion through activation of p21-activated kinase (PAK1) in
RT   pancreatic beta-Cells.";
RL   J. Biol. Chem. 287:26435-26444(2012).
RN   [10]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22798068; DOI=10.1074/jbc.m112.375618;
RA   Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L.,
RA   Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O.,
RA   Yu L.;
RT   "Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively
RT   regulates glucose-stimulated insulin secretion in pancreatic beta-cells.";
RL   J. Biol. Chem. 287:30368-30375(2012).
CC   -!- FUNCTION: Serine/threonine-protein kinase that plays a key role in
CC       polarization of neurons and axonogenesis, cell cycle progress and
CC       insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and
CC       WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a
CC       key regulator of polarization of cortical neurons, probably by
CC       mediating phosphorylation of microtubule-associated proteins such as
CC       MAPT/TAU at 'Thr-504' and 'Ser-554'. Also regulates neuron polarization
CC       by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic
CC       neurons, leading to down-regulate WEE1 activity in polarized neurons.
CC       Plays a role in the regulation of the mitotic cell cycle progress and
CC       the onset of mitosis. Plays a role in the regulation of insulin
CC       secretion in response to elevated glucose levels, probably via
CC       phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-
CC       175 can inhibit insulin secretion (PubMed:22798068), BRSK2
CC       phosphorylated at Thr-261 can promote insulin secretion
CC       (PubMed:22669945). Regulates reorganization of the actin cytoskeleton.
CC       May play a role in the apoptotic response triggered by endoplasmic
CC       reticulum (ER) stress. {ECO:0000269|PubMed:15705853,
CC       ECO:0000269|PubMed:17482548, ECO:0000269|PubMed:20026642,
CC       ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068}.
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:22669945};
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:22669945};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC         COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC         Evidence={ECO:0000269|PubMed:22669945};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC         Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.26; Evidence={ECO:0000269|PubMed:22669945};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-175 by
CC       STK11/LKB1.
CC   -!- SUBUNIT: Interacts with FZR1, a regulatory subunit of the APC ubiquitin
CC       ligase complex. Interacts with COPS5. Interacts with PAK1 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC       center, centrosome {ECO:0000250}. Cytoplasm, perinuclear region
CC       {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Note=Detected at
CC       centrosomes during mitosis. Localizes to the endoplasmic reticulum in
CC       response to stress caused by tunicamycin (By similarity).
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q69Z98-1; Sequence=Displayed;
CC       Name=2; Synonyms=SADA-beta;
CC         IsoId=Q69Z98-2; Sequence=VSP_022605;
CC       Name=3; Synonyms=SADA-gamma;
CC         IsoId=Q69Z98-3; Sequence=VSP_022606;
CC       Name=4; Synonyms=SADA-alpha;
CC         IsoId=Q69Z98-4; Sequence=VSP_022607, VSP_022608;
CC   -!- TISSUE SPECIFICITY: Detected in pancreas islets and in brain (at
CC       protein level). Detected in brain and pancreas.
CC       {ECO:0000269|PubMed:22798068}.
CC   -!- DOMAIN: The KEN box motif is required for interaction with FZR1/CDH1
CC       and essential for APC(CDH1)-mediated ubiquitination. {ECO:0000250}.
CC   -!- PTM: May be phosphorylated at Thr-261 by PKA (By similarity).
CC       Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related
CC       adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at
CC       Thr-175 by CaMKK2. In contrast, it is phosphorylated and activated by
CC       CaMKK1. May be inactivated via dephosphorylation of Thr-175 by PP2C.
CC       {ECO:0000250, ECO:0000269|PubMed:17482548}.
CC   -!- PTM: Polyubiquitinated by the APC complex in conjunction with FZR1,
CC       leading to its proteasomal degradation. Targeted for proteasomal
CC       degradation by interaction with COPS5. BRSK2 levels change during the
CC       cell cycle. BRSK2 levels are low at the G1/S boundary and gradually
CC       increase as cells progress into G2 phase. BRSK2 levels decrease rapidly
CC       at the end of mitosis (By similarity). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are fertile and
CC       healthy. In contrast, mice lacking both Brsk1 and Brsk2 show little
CC       spontaneous movement and are only weakly responsive to tactile
CC       stimulation: they die within 2 hours of birth. Defects are due to
CC       impaired neuronal differentiation and polarity.
CC       {ECO:0000269|PubMed:15705853}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC       protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR   EMBL; AY533672; AAT08447.1; -; mRNA.
DR   EMBL; AY533673; AAT08448.1; -; mRNA.
DR   EMBL; AY533674; AAT08449.1; -; mRNA.
DR   EMBL; AY660739; AAT74618.1; -; mRNA.
DR   EMBL; AL603836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL772165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK173268; BAD32546.1; -; mRNA.
DR   EMBL; BC056498; AAH56498.1; -; mRNA.
DR   CCDS; CCDS22021.1; -. [Q69Z98-4]
DR   CCDS; CCDS22022.1; -. [Q69Z98-3]
DR   CCDS; CCDS22023.1; -. [Q69Z98-2]
DR   RefSeq; NP_001009929.1; NM_001009929.3. [Q69Z98-2]
DR   RefSeq; NP_001009930.1; NM_001009930.3. [Q69Z98-3]
DR   RefSeq; NP_083702.1; NM_029426.2. [Q69Z98-4]
DR   PDB; 4YNZ; X-ray; 2.00 A; A/B=15-342.
DR   PDB; 4YOM; X-ray; 2.49 A; A=519-662, B=1-342.
DR   PDBsum; 4YNZ; -.
DR   PDBsum; 4YOM; -.
DR   AlphaFoldDB; Q69Z98; -.
DR   SMR; Q69Z98; -.
DR   BioGRID; 217728; 67.
DR   STRING; 10090.ENSMUSP00000074969; -.
DR   iPTMnet; Q69Z98; -.
DR   PhosphoSitePlus; Q69Z98; -.
DR   SwissPalm; Q69Z98; -.
DR   MaxQB; Q69Z98; -.
DR   PaxDb; 10090-ENSMUSP00000134201; -.
DR   PeptideAtlas; Q69Z98; -.
DR   ProteomicsDB; 273769; -. [Q69Z98-1]
DR   ProteomicsDB; 273770; -. [Q69Z98-2]
DR   ProteomicsDB; 273771; -. [Q69Z98-3]
DR   ProteomicsDB; 273772; -. [Q69Z98-4]
DR   Pumba; Q69Z98; -.
DR   Antibodypedia; 22872; 263 antibodies from 34 providers.
DR   DNASU; 75770; -.
DR   Ensembl; ENSMUST00000018971.15; ENSMUSP00000018971.9; ENSMUSG00000053046.17. [Q69Z98-4]
DR   Ensembl; ENSMUST00000075528.12; ENSMUSP00000074969.6; ENSMUSG00000053046.17. [Q69Z98-3]
DR   Ensembl; ENSMUST00000078200.12; ENSMUSP00000077330.6; ENSMUSG00000053046.17. [Q69Z98-2]
DR   Ensembl; ENSMUST00000105989.9; ENSMUSP00000101610.3; ENSMUSG00000053046.17. [Q69Z98-2]
DR   Ensembl; ENSMUST00000174499.8; ENSMUSP00000134201.2; ENSMUSG00000053046.17. [Q69Z98-1]
DR   GeneID; 75770; -.
DR   KEGG; mmu:75770; -.
DR   UCSC; uc009kme.2; mouse. [Q69Z98-2]
DR   UCSC; uc009kmf.2; mouse. [Q69Z98-3]
DR   UCSC; uc009kmg.1; mouse. [Q69Z98-4]
DR   UCSC; uc009kmi.1; mouse. [Q69Z98-1]
DR   AGR; MGI:1923020; -.
DR   CTD; 9024; -.
DR   MGI; MGI:1923020; Brsk2.
DR   VEuPathDB; HostDB:ENSMUSG00000053046; -.
DR   eggNOG; KOG0588; Eukaryota.
DR   GeneTree; ENSGT00940000157462; -.
DR   HOGENOM; CLU_000288_156_2_1; -.
DR   InParanoid; Q69Z98; -.
DR   OMA; DTHCVPV; -.
DR   OrthoDB; 5475340at2759; -.
DR   PhylomeDB; Q69Z98; -.
DR   TreeFam; TF313967; -.
DR   BioGRID-ORCS; 75770; 3 hits in 81 CRISPR screens.
DR   PRO; PR:Q69Z98; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q69Z98; Protein.
DR   Bgee; ENSMUSG00000053046; Expressed in visual cortex and 122 other cell types or tissues.
DR   ExpressionAtlas; Q69Z98; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0150034; C:distal axon; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR   GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0030036; P:actin cytoskeleton organization; ISO:MGI.
DR   GO; GO:0007409; P:axonogenesis; IMP:UniProtKB.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0036503; P:ERAD pathway; ISO:MGI.
DR   GO; GO:0030010; P:establishment of cell polarity; IMP:UniProtKB.
DR   GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:MGI.
DR   GO; GO:0090176; P:microtubule cytoskeleton organization involved in establishment of planar polarity; IGI:ARUK-UCL.
DR   GO; GO:0030182; P:neuron differentiation; IGI:UniProtKB.
DR   GO; GO:0048812; P:neuron projection morphogenesis; IGI:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0050770; P:regulation of axonogenesis; IGI:ARUK-UCL.
DR   GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR   GO; GO:0010975; P:regulation of neuron projection development; IGI:ARUK-UCL.
DR   CDD; cd14081; STKc_BRSK1_2; 1.
DR   CDD; cd14340; UBA_BRSK; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR048622; BRSK1_2-like_UBA.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1.
DR   PANTHER; PTHR24346:SF99; SERINE_THREONINE-PROTEIN KINASE BRSK2-LIKE ISOFORM X1; 1.
DR   Pfam; PF21122; KA1_BRSK; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF21115; UBA_BRSK; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q69Z98; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW   Cell division; Cytoplasm; Cytoskeleton; Endoplasmic reticulum; Exocytosis;
KW   Kinase; Magnesium; Metal-binding; Mitosis; Neurogenesis;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN           1..735
FT                   /note="Serine/threonine-protein kinase BRSK2"
FT                   /id="PRO_0000274036"
FT   DOMAIN          20..271
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          298..340
FT                   /note="UBA"
FT   REGION          346..476
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          492..516
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          682..735
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           604..606
FT                   /note="KEN box"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        346..385
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        408..429
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        430..470
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        142
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         26..34
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         49
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         175
FT                   /note="Phosphothreonine; by LKB1"
FT                   /evidence="ECO:0000269|PubMed:17482548"
FT   MOD_RES         261
FT                   /note="Phosphothreonine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWQ3"
FT   MOD_RES         295
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:D3ZML2"
FT   MOD_RES         368
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWQ3"
FT   MOD_RES         383
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         394
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         413
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         424
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         428
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         456
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         460
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         464
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         510
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         513
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         514
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         521
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   VAR_SEQ         648..735
FT                   /note="DTTNCMEVMTGRLSKCGTPLSNFFDVIKQLFSDEKNGQAAQAPSTPAKRSAH
FT                   GPLGDSAAAGPGGDTEYPMGKDMAKMGPPAARREQP -> EPPPPAPGLSWGAGLKGQK
FT                   VATSYESSL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15705853"
FT                   /id="VSP_022605"
FT   VAR_SEQ         648..653
FT                   /note="DTTNCM -> GIIPKS (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:15705853, ECO:0000303|Ref.2"
FT                   /id="VSP_022607"
FT   VAR_SEQ         654..735
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:15705853, ECO:0000303|Ref.2"
FT                   /id="VSP_022608"
FT   VAR_SEQ         664..679
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15705853"
FT                   /id="VSP_022606"
FT   MUTAGEN         49
FT                   /note="K->A: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:15705853"
FT   MUTAGEN         175
FT                   /note="T->A: Prevents phosphorylation and activation by
FT                   STK11/LKB1 complex."
FT                   /evidence="ECO:0000269|PubMed:17482548"
FT   CONFLICT        31..43
FT                   /note="TGLVKLGIHCVTC -> VDGDLLASDTVDS (in Ref. 4;
FT                   BAD32546)"
FT                   /evidence="ECO:0000305"
FT   STRAND          15..17
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          20..29
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          32..39
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   TURN            40..42
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          45..53
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           58..71
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          82..87
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          89..96
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           104..111
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           116..135
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           145..147
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          156..158
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           164..166
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          172..174
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   HELIX           180..182
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           185..188
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           195..212
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           222..231
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           242..251
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   TURN            256..258
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           262..266
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           269..272
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   TURN            274..276
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           296..298
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           301..308
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           311..313
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   HELIX           316..324
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          325..327
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   HELIX           330..342
FT                   /evidence="ECO:0007829|PDB:4YNZ"
FT   STRAND          520..523
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   TURN            524..526
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          530..532
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          534..539
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   HELIX           544..556
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          561..567
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          570..575
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          588..596
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   STRAND          609..618
FT                   /evidence="ECO:0007829|PDB:4YOM"
FT   HELIX           620..635
FT                   /evidence="ECO:0007829|PDB:4YOM"
SQ   SEQUENCE   735 AA;  81733 MW;  A37FCC6CC7253F11 CRC64;
     MTSTGKDGGG AQHAQYVGPY RLEKTLGKGQ TGLVKLGIHC VTCQKVAIKI VNREKLSESV
     LMKVEREIAI LKLIEHPHVL KLHDVYENKK YLYLVLEHVS GGELFDYLVK KGRLTPKEAR
     KFFRQIISAL DFCHSHSICH RDLKPENLLL DERNNIRIAD FGMASLQVGD SLLETSCGSP
     HYACPEVIRG EKYDGRKADV WSCGVILFAL LVGALPFDDD NLRQLLEKVK RGVFHMPHFI
     PPDCQSLLRG MIEVDAARRL TLEHIQKHIW YIGGKNEPEP EQPIPRKVQI RSLPSLEDID
     PDVLDSMHSL GCFRDRNKLL QDLLSEEENQ EKMIYFLLLD RKERYPSHED EDLPPRNEID
     PPRKRVDSPM LNRHGKRRPE RKSMEVLSVT DGGSPVPARR AIEMAQHGQR SRSISGASSG
     LSTSPLSSPR VTPHPSPRGS PLPTPKGTPV HTPKESPAGT PNPTPPSSPS VGGVPWRTRL
     NSIKNSFLGS PRFHRRKLQV PTPEEMSNLT PESSPELAKK SWFGNFINLE KEEQIFVVIK
     DKPLSSIKAD IVHAFLSIPS LSHSVISQTS FRAEYKATGG PAVFQKPVKF QVDITYTEGG
     EAQKENGIYS VTFTLLSGPS RRFKRVVETI QAQLLSTHDQ PSAQHLSDTT NCMEVMTGRL
     SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG PLGDSAAAGP GGDTEYPMGK
     DMAKMGPPAA RREQP
//