BRSK2_RAT
ID BRSK2_RAT Reviewed; 735 AA.
AC D3ZML2; E9PTC7; Q4A1P4;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 81.
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=Sada;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-457 (ISOFORM 2).
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Sabater L., Gomez-Choco M., Saiz A., Graus F.;
RT "BR serine/threonine Kinase 2: a new autoantigen in paraneoplastic limbic
RT encephalitis.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP REGULATION OF TRANSLATION.
RX PubMed=18794346; DOI=10.1101/gad.1685008;
RA Choi Y.J., Di Nardo A., Kramvis I., Meikle L., Kwiatkowski D.J., Sahin M.,
RA He X.;
RT "Tuberous sclerosis complex proteins control axon formation.";
RL Genes Dev. 22:2485-2495(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295; SER-383; SER-394;
RP SER-424; SER-428 AND SER-456, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-417 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(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-523' and 'Ser-573'. 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, BRSK2 phosphorylated at Thr-261 can
CC promote insulin secretion. Regulates reorganization of the actin
CC cytoskeleton. May play a role in the apoptotic response triggered by
CC endoplasmic reticulum (ER) stress (By similarity). {ECO:0000250}.
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-175 by
CC STK11/LKB1. {ECO:0000250}.
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=2;
CC Name=1;
CC IsoId=D3ZML2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=D3ZML2-2; Sequence=VSP_041747;
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 (By
CC similarity). {ECO:0000250}.
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 -!- MISCELLANEOUS: Protein synthesis is inhibited by the TSC1-TSC2 complex
CC acting through TORC1 in neurons, leading to regulate neuron
CC polarization. {ECO:0000305|PubMed:18794346}.
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; AM040976; CAJ13860.1; -; mRNA.
DR AlphaFoldDB; D3ZML2; -.
DR SMR; D3ZML2; -.
DR IntAct; D3ZML2; 1.
DR STRING; 10116.ENSRNOP00000051751; -.
DR iPTMnet; D3ZML2; -.
DR PhosphoSitePlus; D3ZML2; -.
DR SwissPalm; D3ZML2; -.
DR PaxDb; D3ZML2; -.
DR PRIDE; D3ZML2; -.
DR Ensembl; ENSRNOT00000027134; ENSRNOP00000027134; ENSRNOG00000020021. [D3ZML2-2]
DR RGD; 1566256; Brsk2.
DR eggNOG; KOG0588; Eukaryota.
DR InParanoid; D3ZML2; -.
DR PhylomeDB; D3ZML2; -.
DR TreeFam; TF313967; -.
DR PRO; PR:D3ZML2; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0150034; C:distal axon; IMP:ARUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0036503; P:ERAD pathway; ISO:RGD.
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; ISO:RGD.
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:RGD.
DR GO; GO:0090176; P:microtubule cytoskeleton organization involved in establishment of planar polarity; ISO:RGD.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; ISO:RGD.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
DR GO; GO:0009411; P:response to UV; ISS:UniProtKB.
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..735
FT /note="Serine/threonine-protein kinase BRSK2"
FT /id="PRO_0000412650"
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 493..514
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 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:0000250|UniProtKB:Q8IWQ3"
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:0007744|PubMed:22673903"
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:22673903"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IWQ3"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 460
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z98"
FT MOD_RES 464
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z98"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8IWQ3"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z98"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z98"
FT VAR_SEQ 409
FT /note="Q -> QSKAVFSKSLDIAEAHPQFSKED (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_041747"
FT CONFLICT 383
FT /note="S -> C (in Ref. 2; CAJ13860)"
FT /evidence="ECO:0000305"
FT MOD_RES D3ZML2-2:417
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 735 AA; 81455 MW; F5B7958D753BDB04 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 PESSPELGHL QLFGNPVSKV RSVAMELVIL
VQTLAYTSFR LLGTFLPVRY LRHSVLSRPP ERARLVLRGA PCTHMGPVWN MVGMAYTQNP
PIMGETGVYG SQWVMSSAPS KHYTSLGLSV PSPSCSLSPS LFPFCAPDTT NCMEVMTGRL
SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG PLGDSAAAGP GGDTEYPMGK
DMAKMGPPAA RREQP
