ID BRSK2_HUMAN Reviewed; 736 AA. AC Q8IWQ3; B3KVE9; E9PLM7; O60843; O95099; Q5J5B4; Q6ZMQ4; Q8TB60; DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 196. DE RecName: Full=Serine/threonine-protein kinase BRSK2; DE EC=2.7.11.1; DE AltName: Full=Brain-selective kinase 2; 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 29; DE AltName: Full=Serine/threonine-protein kinase SAD-A; GN Name=BRSK2; Synonyms=C11orf7, PEN11B, SADA, STK29; ORFNames=HUSSY-12; 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 4). 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain; RA Guo J.H., Yu L.; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORS 5 AND 6). RC TISSUE=Amygdala; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 72-736 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=11124703; RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h; RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., RA Zimbello R., Lanfranchi G., Valle G.; RT "Characterization of 16 novel human genes showing high similarity to yeast RT sequences."; RL Yeast 18:69-80(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-736 (ISOFORM 2). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 463-736 (ISOFORM 3). RX PubMed=9929968; DOI=10.1007/s100380050096; RA Miura K., Miyoshi O., Yun K., Inazawa J., Miyamoto T., Hayashi H., RA Masuzaki H., Yoshimura S., Niikawa N., Jinno Y., Ishimaru T.; RT "Repeat-directed isolation of a novel gene preferentially expressed from RT the maternal allele in human placenta."; RL J. Hum. Genet. 44:1-9(1999). RN [8] RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-174, AND MUTAGENESIS RP OF THR-174. 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 [9] RP PHOSPHORYLATION AT THR-260, AND MUTAGENESIS OF THR-260. RX PubMed=16870137; DOI=10.1016/j.bbrc.2006.06.178; RA Guo Z., Tang W., Yuan J., Chen X., Wan B., Gu X., Luo K., Wang Y., Yu L.; RT "BRSK2 is activated by cyclic AMP-dependent protein kinase A through RT phosphorylation at Thr260."; RL Biochem. Biophys. Res. Commun. 347:867-871(2006). RN [10] RP PHOSPHORYLATION AT THR-174, AND MUTAGENESIS OF THR-174 AND GLY-310. 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-382 AND SER-393, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 (ISOFORM 4), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-393; SER-412 AND RP THR-509, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] 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 [15] 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 [16] RP INTERACTION WITH COPS5, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=22609399; DOI=10.1016/j.bbrc.2012.05.045; RA Zhou J., Wan B., Li R., Gu X., Zhong Z., Wang Y., Yu L.; RT "Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its RT degradation in the ubiquitin-proteasome pathway."; RL Biochem. Biophys. Res. Commun. 422:647-652(2012). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=22713462; DOI=10.1016/j.bbrc.2012.06.046; RA Wang Y., Wan B., Li D., Zhou J., Li R., Bai M., Chen F., Yu L.; RT "BRSK2 is regulated by ER stress in protein level and involved in ER RT stress-induced apoptosis."; RL Biochem. Biophys. Res. Commun. 423:813-818(2012). RN [18] RP FUNCTION, INTERACTION WITH PAK1, AND MUTAGENESIS OF LYS-48; THR-260 AND RP THR-443. 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 [19] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-48 RP AND THR-174. 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). RN [20] 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 [21] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, INTERACTION WITH FZR1, AND RP DOMAIN KEN BOX MOTIF. RX PubMed=23029325; DOI=10.1371/journal.pone.0045932; RA Li R., Wan B., Zhou J., Wang Y., Luo T., Gu X., Chen F., Yu L.; RT "APC/C(Cdh1) targets brain-specific kinase 2 (BRSK2) for degradation via RT the ubiquitin-proteasome pathway."; RL PLoS ONE 7:E45932-E45932(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-529' and 'Ser-579'. Also regulates neuron polarization CC by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic 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 174 can inhibit insulin secretion (PubMed:22798068), BRSK2 CC phosphorylated at Thr-260 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:14976552, CC ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311, CC ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068, CC ECO:0000269|PubMed:23029325}. 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 -!- 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; 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 -!- 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; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-174 by CC STK11/LKB1. {ECO:0000269|PubMed:14976552}. CC -!- SUBUNIT: Interacts with FZR1, a regulatory subunit of the APC ubiquitin CC ligase complex. Interacts with COPS5. Interacts with PAK1. CC {ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:22669945, CC ECO:0000269|PubMed:23029325}. CC -!- INTERACTION: CC Q8IWQ3; Q92905: COPS5; NbExp=6; IntAct=EBI-3232062, EBI-594661; CC Q8IWQ3; P62258: YWHAE; NbExp=2; IntAct=EBI-3232062, EBI-356498; CC Q8IWQ3-3; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-13085322, EBI-359276; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome. Cytoplasm, perinuclear region. Endoplasmic CC reticulum. Note=Detected at centrosomes during mitosis. Localizes to CC the endoplasmic reticulum in response to stress caused by tunicamycin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q8IWQ3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IWQ3-2; Sequence=VSP_008154, VSP_008155; CC Name=3; CC IsoId=Q8IWQ3-3; Sequence=VSP_008156, VSP_008157; CC Name=4; CC IsoId=Q8IWQ3-4; Sequence=VSP_013945, VSP_008154, VSP_008155; CC Name=5; CC IsoId=Q8IWQ3-5; Sequence=VSP_022603, VSP_022604; CC Name=6; CC IsoId=Q8IWQ3-6; Sequence=VSP_055679, VSP_008154, VSP_008155; CC -!- TISSUE SPECIFICITY: Detected in pancreas islets (at protein level). 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. CC {ECO:0000269|PubMed:23029325}. CC -!- PTM: Phosphorylated at Thr-174 by STK11/LKB1 in complex with STE20- CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Not CC phosphorylated at Thr-174 by CaMKK2. In contrast, it is phosphorylated CC and activated by CaMKK1. May be inactivated via dephosphorylation of CC Thr-174 by PP2C. Phosphorylated at Thr-260 by PKA. Phosphorylation at CC Thr-260 by PKA was not observed in another study (PubMed:18339622), but CC this may reflect differences in the experimental approach. CC Phosphorylation at Thr-260 seems to play a role in the regulation of CC insulin secretion (PubMed:22669945). {ECO:0000269|PubMed:14976552, CC ECO:0000269|PubMed:16870137, ECO:0000269|PubMed:18339622, CC ECO:0000269|PubMed:19958286, ECO:0000269|PubMed:22669945}. 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. {ECO:0000269|PubMed:22609399, CC ECO:0000269|PubMed:23029325}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD09654.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAD09654.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH24291.1; 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; AY505125; AAS86443.1; -; mRNA. DR EMBL; AF533876; AAP97723.1; -; mRNA. DR EMBL; AF533877; AAP97724.1; -; mRNA. DR EMBL; AF533878; AAP97725.1; -; mRNA. DR EMBL; AF533879; AAP97726.1; -; mRNA. DR EMBL; AF533880; AAP97727.1; -; mRNA. DR EMBL; AY166857; AAN87839.1; -; mRNA. DR EMBL; AK122851; BAG53761.1; -; mRNA. DR EMBL; AK131534; BAD18671.1; -; mRNA. DR EMBL; AC091196; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC136297; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ006701; CAA07196.1; -; mRNA. DR EMBL; BC024291; AAH24291.1; ALT_INIT; mRNA. DR EMBL; AF020089; AAD09654.1; ALT_SEQ; mRNA. DR CCDS; CCDS41590.1; -. [Q8IWQ3-3] DR CCDS; CCDS58106.1; -. [Q8IWQ3-2] DR CCDS; CCDS58107.1; -. [Q8IWQ3-1] DR CCDS; CCDS58108.1; -. [Q8IWQ3-5] DR CCDS; CCDS60696.1; -. [Q8IWQ3-6] DR RefSeq; NP_001243556.1; NM_001256627.1. [Q8IWQ3-1] DR RefSeq; NP_001243558.1; NM_001256629.1. [Q8IWQ3-2] DR RefSeq; NP_001243559.1; NM_001256630.1. [Q8IWQ3-5] DR RefSeq; NP_001269147.1; NM_001282218.1. [Q8IWQ3-6] DR RefSeq; NP_003948.2; NM_003957.3. [Q8IWQ3-3] DR AlphaFoldDB; Q8IWQ3; -. DR SMR; Q8IWQ3; -. DR BioGRID; 114491; 25. DR IntAct; Q8IWQ3; 10. DR MINT; Q8IWQ3; -. DR STRING; 9606.ENSP00000371614; -. DR BindingDB; Q8IWQ3; -. DR ChEMBL; CHEMBL4574; -. DR DrugCentral; Q8IWQ3; -. DR GuidetoPHARMACOLOGY; 1947; -. DR GlyGen; Q8IWQ3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8IWQ3; -. DR PhosphoSitePlus; Q8IWQ3; -. DR BioMuta; BRSK2; -. DR DMDM; 116241272; -. DR CPTAC; non-CPTAC-6014; -. DR CPTAC; non-CPTAC-6015; -. DR EPD; Q8IWQ3; -. DR jPOST; Q8IWQ3; -. DR MassIVE; Q8IWQ3; -. DR MaxQB; Q8IWQ3; -. DR PaxDb; 9606-ENSP00000371614; -. DR PeptideAtlas; Q8IWQ3; -. DR ProteomicsDB; 21843; -. DR ProteomicsDB; 70877; -. [Q8IWQ3-1] DR ProteomicsDB; 70878; -. [Q8IWQ3-2] DR ProteomicsDB; 70879; -. [Q8IWQ3-3] DR ProteomicsDB; 70880; -. [Q8IWQ3-4] DR ProteomicsDB; 70881; -. [Q8IWQ3-5] DR Pumba; Q8IWQ3; -. DR Antibodypedia; 22872; 263 antibodies from 34 providers. DR DNASU; 9024; -. DR Ensembl; ENST00000308219.13; ENSP00000310697.9; ENSG00000174672.16. [Q8IWQ3-3] DR Ensembl; ENST00000382179.5; ENSP00000371614.1; ENSG00000174672.16. [Q8IWQ3-5] DR Ensembl; ENST00000526678.5; ENSP00000433370.1; ENSG00000174672.16. [Q8IWQ3-4] DR Ensembl; ENST00000528710.5; ENSP00000433235.1; ENSG00000174672.16. [Q8IWQ3-6] DR Ensembl; ENST00000528841.6; ENSP00000432000.1; ENSG00000174672.16. [Q8IWQ3-1] DR Ensembl; ENST00000529433.5; ENSP00000433684.1; ENSG00000174672.16. [Q8IWQ3-2] DR Ensembl; ENST00000531197.5; ENSP00000431152.1; ENSG00000174672.16. [Q8IWQ3-2] DR Ensembl; ENST00000707533.1; ENSP00000516897.1; ENSG00000291428.1. [Q8IWQ3-3] DR Ensembl; ENST00000707534.1; ENSP00000516898.1; ENSG00000291428.1. [Q8IWQ3-2] DR Ensembl; ENST00000707535.1; ENSP00000516899.1; ENSG00000291428.1. [Q8IWQ3-1] DR Ensembl; ENST00000707536.1; ENSP00000516900.1; ENSG00000291428.1. [Q8IWQ3-2] DR Ensembl; ENST00000707537.1; ENSP00000516901.1; ENSG00000291428.1. [Q8IWQ3-4] DR Ensembl; ENST00000707540.1; ENSP00000516904.1; ENSG00000291428.1. [Q8IWQ3-6] DR Ensembl; ENST00000707541.1; ENSP00000516905.1; ENSG00000291428.1. [Q8IWQ3-5] DR GeneID; 9024; -. DR KEGG; hsa:9024; -. DR MANE-Select; ENST00000528841.6; ENSP00000432000.1; NM_001256627.2; NP_001243556.1. DR UCSC; uc001lti.5; human. [Q8IWQ3-1] DR AGR; HGNC:11405; -. DR CTD; 9024; -. DR DisGeNET; 9024; -. DR GeneCards; BRSK2; -. DR HGNC; HGNC:11405; BRSK2. DR HPA; ENSG00000174672; Group enriched (brain, pancreas). DR MalaCards; BRSK2; -. DR MIM; 609236; gene. DR neXtProt; NX_Q8IWQ3; -. DR OpenTargets; ENSG00000174672; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR PharmGKB; PA36212; -. DR VEuPathDB; HostDB:ENSG00000174672; -. DR eggNOG; KOG0588; Eukaryota. DR GeneTree; ENSGT00940000157462; -. DR HOGENOM; CLU_000288_156_2_1; -. DR InParanoid; Q8IWQ3; -. DR OMA; DTHCVPV; -. DR OrthoDB; 5475340at2759; -. DR PhylomeDB; Q8IWQ3; -. DR TreeFam; TF313967; -. DR PathwayCommons; Q8IWQ3; -. DR SignaLink; Q8IWQ3; -. DR SIGNOR; Q8IWQ3; -. DR BioGRID-ORCS; 9024; 9 hits in 1181 CRISPR screens. DR ChiTaRS; BRSK2; human. DR GeneWiki; BRSK2; -. DR GenomeRNAi; 9024; -. DR Pharos; Q8IWQ3; Tchem. DR PRO; PR:Q8IWQ3; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q8IWQ3; Protein. DR Bgee; ENSG00000174672; Expressed in right hemisphere of cerebellum and 108 other cell types or tissues. DR ExpressionAtlas; Q8IWQ3; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0150034; C:distal axon; ISS:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0051117; F:ATPase binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0060590; F:ATPase regulator activity; NAS:ParkinsonsUK-UCL. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. 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:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB. DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB. 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; IMP:UniProtKB. DR GO; GO:0090176; P:microtubule cytoskeleton organization involved in establishment of planar polarity; ISS:ARUK-UCL. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0043462; P:regulation of ATP-dependent activity; NAS:ParkinsonsUK-UCL. DR GO; GO:0050770; P:regulation of axonogenesis; ISS: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; ISS:ARUK-UCL. DR GO; GO:1904152; P:regulation of retrograde protein transport, ER to cytosol; NAS:ParkinsonsUK-UCL. DR GO; GO:2000807; P:regulation of synaptic vesicle clustering; TAS: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; Q8IWQ3; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell division; KW Cytoplasm; Cytoskeleton; Endoplasmic reticulum; Exocytosis; Kinase; KW Magnesium; Metal-binding; Mitosis; Neurogenesis; Nucleotide-binding; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Ubl conjugation. FT CHAIN 1..736 FT /note="Serine/threonine-protein kinase BRSK2" FT /id="PRO_0000085670" FT DOMAIN 19..270 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 297..339 FT /note="UBA" FT REGION 345..475 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 493..513 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 681..736 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 603..605 FT /note="KEN box" FT COMPBIAS 345..384 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 407..428 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 429..469 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 141 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 25..33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 48 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 174 FT /note="Phosphothreonine; by LKB1" FT /evidence="ECO:0000269|PubMed:14976552, FT ECO:0000269|PubMed:18339622" FT MOD_RES 260 FT /note="Phosphothreonine; by PKA" FT /evidence="ECO:0000269|PubMed:16870137" FT MOD_RES 294 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D3ZML2" FT MOD_RES 367 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 382 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332" FT MOD_RES 412 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 427 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 455 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 459 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 463 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 509 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 513 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT MOD_RES 520 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q69Z98" FT VAR_SEQ 1..60 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_055679" FT VAR_SEQ 1..30 FT /note="MTSTGKDGGAQHAQYVGPYRLEKTLGKGQT -> MSPEGHPSRWARPRRPCI FT CPSSLCSPREPRSGPAVGRGGAAHHRVPAGHTPGPQLLQPHLHLPQGQTWLCLQPSPA FT (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_022603" FT VAR_SEQ 408 FT /note="Q -> QSKAMFSKSLDIAEAHPQFSKED (in isoform 4)" FT /evidence="ECO:0000303|PubMed:16630837" FT /id="VSP_013945" FT VAR_SEQ 647..674 FT /note="DTTNCMEMMTGRLSKCGSPLSNFFDVIK -> EPPPPAPGLSWGAGLKGQKV FT ATSYESSL (in isoform 2, isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:11124703, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16630837, FT ECO:0000303|Ref.2" FT /id="VSP_008154" FT VAR_SEQ 663..678 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_022604" FT VAR_SEQ 664..668 FT /note="SPLSN -> IIPKS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9929968, ECO:0000303|Ref.2" FT /id="VSP_008156" FT VAR_SEQ 669..736 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9929968, ECO:0000303|Ref.2" FT /id="VSP_008157" FT VAR_SEQ 675..736 FT /note="Missing (in isoform 2, isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:11124703, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16630837, FT ECO:0000303|Ref.2" FT /id="VSP_008155" FT MUTAGEN 48 FT /note="K->M: Loss of catalytic activity. Causes FT disintegration of actin stress fibers." FT /evidence="ECO:0000269|PubMed:22669945, FT ECO:0000269|PubMed:22798068" FT MUTAGEN 174 FT /note="T->A: Prevents phosphorylation and activation by FT STK11/LKB1 complex." FT /evidence="ECO:0000269|PubMed:14976552, FT ECO:0000269|PubMed:18339622, ECO:0000269|PubMed:22798068" FT MUTAGEN 174 FT /note="T->E: Constitutively activated." FT /evidence="ECO:0000269|PubMed:14976552, FT ECO:0000269|PubMed:18339622, ECO:0000269|PubMed:22798068" FT MUTAGEN 260 FT /note="T->A: Decreased phosphorylation. Nearly abolishes FT stimulation of insulin secretion." FT /evidence="ECO:0000269|PubMed:16870137, FT ECO:0000269|PubMed:22669945" FT MUTAGEN 310 FT /note="G->A: Decreased activation of kinase activity." FT /evidence="ECO:0000269|PubMed:18339622" FT MUTAGEN 443 FT /note="T->A: Constitutively activated. Promotes formation FT of actin stress fibers." FT /evidence="ECO:0000269|PubMed:22669945" FT CONFLICT 251 FT /note="I -> S (in Ref. 2; FT AAP97723/AAP97724/AAP97725/AAP97726/AAP97727/AAN87839 and FT 5; CAA07196)" FT /evidence="ECO:0000305" FT CONFLICT 409 FT /note="R -> G (in Ref. 3; BAG53761)" FT /evidence="ECO:0000305" FT MOD_RES Q8IWQ3-4:416 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" SQ SEQUENCE 736 AA; 81633 MW; D9EBA511149449E6 CRC64; MTSTGKDGGA QHAQYVGPYR LEKTLGKGQT GLVKLGVHCV TCQKVAIKIV NREKLSESVL MKVEREIAIL KLIEHPHVLK LHDVYENKKY LYLVLEHVSG GELFDYLVKK GRLTPKEARK FFRQIISALD FCHSHSICHR DLKPENLLLD EKNNIRIADF GMASLQVGDS LLETSCGSPH YACPEVIRGE KYDGRKADVW SCGVILFALL VGALPFDDDN LRQLLEKVKR GVFHMPHFIP PDCQSLLRGM IEVDAARRLT LEHIQKHIWY IGGKNEPEPE QPIPRKVQIR SLPSLEDIDP DVLDSMHSLG CFRDRNKLLQ DLLSEEENQE KMIYFLLLDR KERYPSQEDE DLPPRNEIDP PRKRVDSPML NRHGKRRPER KSMEVLSVTD GGSPVPARRA IEMAQHGQRS RSISGASSGL STSPLSSPRV TPHPSPRGSP LPTPKGTPVH TPKESPAGTP NPTPPSSPSV GGVPWRARLN SIKNSFLGSP RFHRRKLQVP TPEEMSNLTP ESSPELAKKS WFGNFISLEK EEQIFVVIKD KPLSSIKADI VHAFLSIPSL SHSVISQTSF RAEYKATGGP AVFQKPVKFQ VDITYTEGGE AQKENGIYSV TFTLLSGPSR RFKRVVETIQ AQLLSTHDPP AAQHLSDTTN CMEMMTGRLS KCGSPLSNFF DVIKQLFSDE KNGQAAQAPS TPAKRSAHGP LGDSAAAGPG PGGDAEYPTG KDTAKMGPPT ARREQP //