BRSK2_MOUSE
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 03-AUG-2022, entry version 148.
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; 8.
DR STRING; 10090.ENSMUSP00000134201; -.
DR iPTMnet; Q69Z98; -.
DR PhosphoSitePlus; Q69Z98; -.
DR SwissPalm; Q69Z98; -.
DR MaxQB; Q69Z98; -.
DR PaxDb; Q69Z98; -.
DR PeptideAtlas; Q69Z98; -.
DR PRIDE; Q69Z98; -.
DR ProteomicsDB; 273769; -. [Q69Z98-1]
DR ProteomicsDB; 273770; -. [Q69Z98-2]
DR ProteomicsDB; 273771; -. [Q69Z98-3]
DR ProteomicsDB; 273772; -. [Q69Z98-4]
DR Antibodypedia; 22872; 227 antibodies from 34 providers.
DR DNASU; 75770; -.
DR Ensembl; ENSMUST00000018971; ENSMUSP00000018971; ENSMUSG00000053046. [Q69Z98-4]
DR Ensembl; ENSMUST00000075528; ENSMUSP00000074969; ENSMUSG00000053046. [Q69Z98-3]
DR Ensembl; ENSMUST00000078200; ENSMUSP00000077330; ENSMUSG00000053046. [Q69Z98-2]
DR Ensembl; ENSMUST00000105989; ENSMUSP00000101610; ENSMUSG00000053046. [Q69Z98-2]
DR Ensembl; ENSMUST00000174499; ENSMUSP00000134201; ENSMUSG00000053046. [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 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; RKFTTEL; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q69Z98; -.
DR TreeFam; TF313967; -.
DR BioGRID-ORCS; 75770; 3 hits in 76 CRISPR screens.
DR PRO; PR:Q69Z98; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q69Z98; protein.
DR Bgee; ENSMUSG00000053046; Expressed in visual cortex and 120 other tissues.
DR ExpressionAtlas; Q69Z98; baseline and differential.
DR Genevisible; Q69Z98; MM.
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:0031532; P:actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
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:0018105; P:peptidyl-serine phosphorylation; IDA: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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 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
