BRSK2_HUMAN
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 03-AUG-2022, entry version 187.
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 Q8IWQ3-3; 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};
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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; 19.
DR IntAct; Q8IWQ3; 7.
DR STRING; 9606.ENSP00000371614; -.
DR BindingDB; Q8IWQ3; -.
DR ChEMBL; CHEMBL4574; -.
DR DrugCentral; Q8IWQ3; -.
DR GuidetoPHARMACOLOGY; 1947; -.
DR iPTMnet; Q8IWQ3; -.
DR PhosphoSitePlus; Q8IWQ3; -.
DR BioMuta; BRSK2; -.
DR DMDM; 116241272; -.
DR EPD; Q8IWQ3; -.
DR jPOST; Q8IWQ3; -.
DR MassIVE; Q8IWQ3; -.
DR MaxQB; Q8IWQ3; -.
DR PaxDb; Q8IWQ3; -.
DR PeptideAtlas; Q8IWQ3; -.
DR PRIDE; 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 Antibodypedia; 22872; 227 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 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 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; RKFTTEL; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q8IWQ3; -.
DR TreeFam; TF313967; -.
DR PathwayCommons; Q8IWQ3; -.
DR SignaLink; Q8IWQ3; -.
DR SIGNOR; Q8IWQ3; -.
DR BioGRID-ORCS; 9024; 8 hits in 1101 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 106 other tissues.
DR ExpressionAtlas; Q8IWQ3; baseline and differential.
DR Genevisible; Q8IWQ3; HS.
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:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; ISS: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; 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:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
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 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 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; AAP97723/AAP97724/AAP97725/
FT AAP97726/AAP97727/AAN87839 and 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
