ID BRSK1_HUMAN Reviewed; 778 AA. AC Q8TDC3; F1DG44; Q5J5B5; Q8NDD0; Q8NDR4; Q8TDC2; Q96AV4; Q96JL4; DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 21-SEP-2011, sequence version 2. DT 12-AUG-2020, entry version 175. DE RecName: Full=Serine/threonine-protein kinase BRSK1; DE EC=2.7.11.1; DE AltName: Full=Brain-selective kinase 1; DE EC=2.7.11.26; DE AltName: Full=Brain-specific serine/threonine-protein kinase 1; DE Short=BR serine/threonine-protein kinase 1; DE AltName: Full=Serine/threonine-protein kinase SAD-B; DE AltName: Full=Synapses of Amphids Defective homolog 1; DE Short=SAD1 homolog; DE Short=hSAD1; GN Name=BRSK1; Synonyms=KIAA1811, SAD1, SADB; 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] (ISOFORM 2), FUNCTION, ACTIVITY REGULATION, RP PHOSPHORYLATION AT THR-189, AND MUTAGENESIS OF THR-189. 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-59. RC TISSUE=Testis; RX PubMed=15150265; DOI=10.1074/jbc.m404728200; RA Lu R., Niida H., Nakanishi M.; RT "Human SAD1 kinase is involved in UV-induced DNA damage checkpoint RT function."; RL J. Biol. Chem. 279:31164-31170(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=16630837; DOI=10.1016/j.neuron.2006.03.018; RA Inoue E., Mochida S., Takagi H., Higa S., Deguchi-Tawarada M., RA Takao-Rikitsu E., Inoue M., Yao I., Takeuchi K., Kitajima I., Setou M., RA Ohtsuka T., Takai Y.; RT "SAD: a presynaptic kinase associated with synaptic vesicles and the active RT zone cytomatrix that regulates neurotransmitter release."; RL Neuron 50:261-275(2006). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=19648910; DOI=10.1038/ncb1921; RA Alvarado-Kristensson M., Rodriguez M.J., Silio V., Valpuesta J.M., RA Carrera A.C.; RT "SADB phosphorylation of gamma-tubulin regulates centrosome duplication."; RL Nat. Cell Biol. 11:1081-1092(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RA She X.Y., Yu L., Guo J.H.; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-778. RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-778. RC TISSUE=Brain; RX PubMed=11347906; DOI=10.1093/dnares/8.2.85; RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 8:85-95(2001). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 287-778. RC TISSUE=Lymph; 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 [10] RP PHOSPHORYLATION AT THR-189, AND MUTAGENESIS OF GLY-327. RX PubMed=18339622; DOI=10.1074/jbc.m710381200; RA Bright N.J., Carling D., Thornton C.; RT "Investigating the regulation of brain-specific kinases 1 and 2 by RT phosphorylation."; RL J. Biol. Chem. 283:14946-14954(2008). RN [11] RP PHOSPHORYLATION. RX PubMed=19958286; DOI=10.1042/bj20091372; RA Fogarty S., Hawley S.A., Green K.A., Saner N., Mustard K.J., Hardie D.G.; RT "Calmodulin-dependent protein kinase kinase-beta activates AMPK without RT forming a stable complex: synergistic effects of Ca2+ and AMP."; RL Biochem. J. 426:109-118(2010). RN [12] 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 [13] RP CATALYTIC ACTIVITY, AND FUNCTION IN MAPT PHOSPHORYLATION. RX PubMed=21985311; DOI=10.1111/j.1471-4159.2011.07523.x; RA Yoshida H., Goedert M.; RT "Phosphorylation of microtubule-associated protein tau by AMPK-related RT kinases."; RL J. Neurochem. 120:165-176(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION BY RP 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 [15] RP VARIANTS [LARGE SCALE ANALYSIS] TRP-303; ILE-319; GLU-391; ASN-531; SER-749 RP AND ALA-764. 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). CC -!- FUNCTION: Serine/threonine-protein kinase that plays a key role in CC polarization of neurons and centrosome duplication. Phosphorylates CC CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following CC phosphorylation and activation by STK11/LKB1, acts as a key regulator CC of polarization of cortical neurons, probably by mediating CC phosphorylation of microtubule-associated proteins such as MAPT/TAU at CC 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by CC mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, CC leading to down-regulate WEE1 activity in polarized neurons. In CC neurons, localizes to synaptic vesicles and plays a role in CC neurotransmitter release, possibly by phosphorylating RIMS1. Also acts CC as a positive regulator of centrosome duplication by mediating CC phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', CC leading to translocation of gamma-tubulin and its associated proteins CC to the centrosome. Involved in the UV-induced DNA damage checkpoint CC response, probably by inhibiting CDK1 activity through phosphorylation CC and activation of WEE1, and inhibition of CDC25B and CDC25C. CC {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15150265, CC ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311}. 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:21985311}; 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:21985311}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[tau protein]-L-serine + ATP = [tau protein]-O-phospho-L- CC serine + ADP + H(+); Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, CC Rhea:RHEA-COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC EC=2.7.11.26; Evidence={ECO:0000269|PubMed:21985311}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[tau protein]-L-threonine + ATP = [tau protein]-O-phospho-L- CC threonine + ADP + H(+); 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:21985311}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-189 by CC STK11/LKB1. {ECO:0000269|PubMed:14976552}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15150265}. Nucleus CC {ECO:0000269|PubMed:15150265}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000250}. Cell junction, synapse CC {ECO:0000250|UniProtKB:B2DD29}. Cell junction, synapse, presynaptic CC active zone {ECO:0000250|UniProtKB:B2DD29}. Cytoplasmic vesicle, CC secretory vesicle, synaptic vesicle {ECO:0000250|UniProtKB:B2DD29}. CC Note=Nuclear in the absence of DNA damage. Translocated to the nucleus CC in response to UV- or MMS-induced DNA damage (By similarity). CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=SADB-Long, L; CC IsoId=Q8TDC3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TDC3-2; Sequence=VSP_008158; CC Name=3; Synonyms=SADB-short, S; CC IsoId=Q8TDC3-3; Sequence=VSP_041742; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in brain and CC testis. Protein levels remain constant throughout the cell cycle. CC {ECO:0000269|PubMed:15150265}. CC -!- PTM: Phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20- CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Not CC phosphorylated at Thr-189 by CaMKK2. In contrast, it is phosphorylated CC and activated by CaMKK1. May be inactivated via dephosphorylation of CC Thr-189 by PP2C. {ECO:0000269|PubMed:14976552, CC ECO:0000269|PubMed:18339622, ECO:0000269|PubMed:19958286}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH16681.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY458602; AAS10354.1; -; mRNA. DR EMBL; AY505124; AAS86442.1; -; mRNA. DR EMBL; HQ830199; ADX95745.1; -; mRNA. DR EMBL; AF479826; AAL87697.1; -; mRNA. DR EMBL; AF479827; AAL87698.1; -; mRNA. DR EMBL; AC008974; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020922; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL831945; CAD38595.1; -; mRNA. DR EMBL; AL834275; CAD38950.2; -; mRNA. DR EMBL; AB058714; BAB47440.1; -; mRNA. DR EMBL; BC016681; AAH16681.1; ALT_INIT; mRNA. DR CCDS; CCDS12921.1; -. [Q8TDC3-1] DR RefSeq; NP_115806.1; NM_032430.1. [Q8TDC3-1] DR SMR; Q8TDC3; -. DR BioGRID; 124084; 7. DR IntAct; Q8TDC3; 3. DR STRING; 9606.ENSP00000310649; -. DR BindingDB; Q8TDC3; -. DR ChEMBL; CHEMBL5650; -. DR DrugCentral; Q8TDC3; -. DR iPTMnet; Q8TDC3; -. DR PhosphoSitePlus; Q8TDC3; -. DR BioMuta; BRSK1; -. DR DMDM; 347595639; -. DR jPOST; Q8TDC3; -. DR MassIVE; Q8TDC3; -. DR PaxDb; Q8TDC3; -. DR PeptideAtlas; Q8TDC3; -. DR PRIDE; Q8TDC3; -. DR ProteomicsDB; 74264; -. [Q8TDC3-1] DR ProteomicsDB; 74265; -. [Q8TDC3-2] DR ProteomicsDB; 74266; -. [Q8TDC3-3] DR Antibodypedia; 19545; 445 antibodies. DR Ensembl; ENST00000309383; ENSP00000310649; ENSG00000160469. [Q8TDC3-1] DR Ensembl; ENST00000585418; ENSP00000467357; ENSG00000160469. [Q8TDC3-3] DR Ensembl; ENST00000590333; ENSP00000468190; ENSG00000160469. [Q8TDC3-2] DR GeneID; 84446; -. DR KEGG; hsa:84446; -. DR UCSC; uc002qkf.4; human. [Q8TDC3-1] DR CTD; 84446; -. DR DisGeNET; 84446; -. DR EuPathDB; HostDB:ENSG00000160469.16; -. DR GeneCards; BRSK1; -. DR HGNC; HGNC:18994; BRSK1. DR HPA; ENSG00000160469; Tissue enriched (brain). DR MIM; 609235; gene. DR neXtProt; NX_Q8TDC3; -. DR OpenTargets; ENSG00000160469; -. DR PharmGKB; PA134888976; -. DR eggNOG; KOG0588; Eukaryota. DR GeneTree; ENSGT00940000161254; -. DR HOGENOM; CLU_000288_156_2_1; -. DR InParanoid; Q8TDC3; -. DR KO; K08796; -. DR OMA; YSYHPEY; -. DR OrthoDB; 1127668at2759; -. DR PhylomeDB; Q8TDC3; -. DR TreeFam; TF313967; -. DR PathwayCommons; Q8TDC3; -. DR SignaLink; Q8TDC3; -. DR SIGNOR; Q8TDC3; -. DR BioGRID-ORCS; 84446; 6 hits in 903 CRISPR screens. DR ChiTaRS; BRSK1; human. DR GeneWiki; BRSK1; -. DR GenomeRNAi; 84446; -. DR Pharos; Q8TDC3; Tchem. DR PRO; PR:Q8TDC3; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q8TDC3; protein. DR Bgee; ENSG00000160469; Expressed in prefrontal cortex and 150 other tissues. DR ExpressionAtlas; Q8TDC3; baseline and differential. DR Genevisible; Q8TDC3; HS. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0150034; C:distal axon; ISS:ARUK-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048786; C:presynaptic active zone; TAS:ARUK-UCL. DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IC:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB. DR GO; GO:0008306; P:associative learning; ISS:ARUK-UCL. DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB. DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IDA:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0090176; P:microtubule cytoskeleton organization involved in establishment of planar polarity; ISS:ARUK-UCL. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint; IDA:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0007269; P:neurotransmitter secretion; ISS:UniProtKB. 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; ISS:ARUK-UCL. DR GO; GO:0010975; P:regulation of neuron projection development; ISS:ARUK-UCL. DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:ARUK-UCL. DR GO; GO:2000807; P:regulation of synaptic vesicle clustering; TAS:ARUK-UCL. DR GO; GO:0009411; P:response to UV; IDA:UniProtKB. DR GO; GO:0099504; P:synaptic vesicle cycle; ISS: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 InterPro; IPR015940; UBA. 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. DR PROSITE; PS50030; UBA; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cell cycle; Cell junction; KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; DNA damage; KW Kinase; Magnesium; Metal-binding; Methylation; Neurogenesis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..778 FT /note="Serine/threonine-protein kinase BRSK1" FT /id="PRO_0000085669" FT DOMAIN 34..285 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 314..356 FT /note="UBA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212" FT NP_BIND 40..48 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT COMPBIAS 492..540 FT /note="Pro-rich" FT ACT_SITE 156 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 63 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 189 FT /note="Phosphothreonine; by LKB1" FT /evidence="ECO:0000269|PubMed:14976552, FT ECO:0000269|PubMed:18339622" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 443 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 447 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 450 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 466 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 481 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 484 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 498 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 508 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 525 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 529 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 535 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 550 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 583 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5RJI5" FT MOD_RES 586 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B2DD29" FT MOD_RES 587 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B2DD29" FT MOD_RES 601 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B2DD29" FT VAR_SEQ 1..26 FT /note="MSSGAKEGGGGSPAYHLPHPHPHPPQ -> MVAGLTLGKGPESPDGDVSVPE FT RKDEVAGGGGEEEEAEERGR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14976552, ECO:0000303|Ref.5" FT /id="VSP_008158" FT VAR_SEQ 344..778 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:19648910" FT /id="VSP_041742" FT VARIANT 303 FT /note="R -> W (in a gastric adenocarcinoma sample; somatic FT mutation; dbSNP:rs144130246)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040394" FT VARIANT 319 FT /note="V -> I (in a lung large cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040395" FT VARIANT 391 FT /note="G -> E (in a metastatic melanoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040396" FT VARIANT 531 FT /note="T -> N (in dbSNP:rs55892637)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040397" FT VARIANT 749 FT /note="G -> S (in dbSNP:rs12978445)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040398" FT VARIANT 764 FT /note="P -> A (in dbSNP:rs55796422)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040399" FT MUTAGEN 59 FT /note="K->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:15150265" FT MUTAGEN 189 FT /note="T->A: Prevents phosphorylation and activation by FT STK11/LKB1 complex." FT /evidence="ECO:0000269|PubMed:14976552" FT MUTAGEN 327 FT /note="G->A: Abolishes activation of kinase activity." FT /evidence="ECO:0000269|PubMed:18339622" FT CONFLICT 762 FT /note="G -> A (in Ref. 9; AAH16681)" FT /evidence="ECO:0000305" SQ SEQUENCE 778 AA; 85087 MW; 8D1818D4E54398BB CRC64; MSSGAKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL GVHCITGQKV AIKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY ENKKYLYLVL EHVSGGELFD YLVKKGRLTP KEARKFFRQI VSALDFCHSY SICHRDLKPE NLLLDEKNNI RIADFGMASL QVGDSLLETS CGSPHYACPE VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL EKVKRGVFHM PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI YYLLLDRKER YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM EVLSITDAGG GGSPVPTRRA LEMAQHSQRS RSVSGASTGL SSSPLSSPRS PVFSFSPEPG AGDEARGGGS PTSKTQTLPS RGPRGGGAGE QPPPPSARST PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP GGGVGGAAWR SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA SGGPSVFQKP VRFQVDISSS EGPEPSPRRD GSGGGGIYSV TFTLISGPSR RFKRVVETIQ AQLLSTHDQP SVQALADEKN GAQTRPAGAP PRSLQPPPGR PDPELSSSPR RGPPKDKKLL ATNGTPLP //