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B2DD29 (BRSK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 44. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase BRSK1

EC=2.7.11.1
EC=2.7.11.26
Alternative name(s):
Brain-specific serine/threonine-protein kinase 1
Short name=BR serine/threonine-protein kinase 1
Serine/threonine-protein kinase SAD-B
Gene names
Name:Brsk1
Synonyms:Sadb
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length778 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-523' and 'Ser-573'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C By similarity. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + [tau protein] = ADP + [tau protein] phosphate.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation on Thr-189 by STK11/LKB1.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cell junctionsynapse. Note: Nuclear in the absence of DNA damage. Translocated to the nucleus in response to UV- or MMS-induced DNA damage By similarity. Localizes to synaptic vesicles in neurons. Ref.3

Tissue specificity

Mainly present in brain. Present in presynaptic nerve terminals (at protein level). Ref.3

Post-translational modification

Phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-189 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-189 by PP2C. May be autophosphorylated. Ref.1 Ref.3

Miscellaneous

Protein synthesis is inhibited by the TSC1-TSC2 complex acting through TORC1 in neurons, leading to regulate neuron polarization (Ref.4).

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Contains 1 UBA domain.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
Neurogenesis
   Cellular componentCell junction
Cytoplasm
Cytoskeleton
Nucleus
Synapse
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2 DNA damage checkpoint

Inferred from electronic annotation. Source: Ensembl

axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome duplication

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

neurotransmitter secretion

Inferred from mutant phenotype Ref.3. Source: UniProtKB

protein autophosphorylation

Traceable author statement Ref.3. Source: UniProtKB

response to UV

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Inferred from direct assay Ref.3. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

gamma-tubulin binding

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

protein serine/threonine kinase activity

Inferred from direct assay Ref.3. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 778778Serine/threonine-protein kinase BRSK1
PRO_0000412649

Regions

Domain34 – 285252Protein kinase
Domain314 – 35643UBA
Nucleotide binding40 – 489ATP By similarity
Compositional bias492 – 54049Pro-rich

Sites

Active site1561Proton acceptor By similarity
Binding site631ATP By similarity

Amino acid modifications

Modified residue1891Phosphothreonine; by LKB1 Ref.1
Modified residue1931Phosphoserine Probable
Modified residue4471Phosphoserine By similarity
Modified residue5081Phosphoserine By similarity
Modified residue5631Phosphoserine By similarity

Experimental info

Mutagenesis631K → R: Abolishes kinase activity. Ref.3
Mutagenesis1891T → A: Decreased autophosphorylation; when associated with A-193. Ref.3
Mutagenesis1931S → A: Decreased autophosphorylation; when associated with A-189. Ref.3

Sequences

Sequence LengthMass (Da)Tools
B2DD29 [UniParc].

Last modified June 10, 2008. Version 1.
Checksum: A4F1E7E107359BDD

FASTA77885,183
        10         20         30         40         50         60 
MSSGSKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL GVHCITGQKV 

        70         80         90        100        110        120 
AVKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY ENKKYLYLVL EHVSGGELFD 

       130        140        150        160        170        180 
YLVKKGRLTP KEARKFFRQI VSALDFCHSY SICHRDLKPE NLLLDEKNNI RIADFGMASL 

       190        200        210        220        230        240 
QVGDSLLETS CGSPHYACPE VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL 

       250        260        270        280        290        300 
EKVKRGVFHM PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP 

       310        320        330        340        350        360 
GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI YYLLLDRKER 

       370        380        390        400        410        420 
YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM EVLSITDAGS GGSPVPTRRA 

       430        440        450        460        470        480 
LEMAQHSQRS RSVSGASTGL SSSPLSSPRS PVFSFSPEPG VGDEARGGGS PTSKTQTLPS 

       490        500        510        520        530        540 
RGPRGGGAGE QPPPPSARST PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP 

       550        560        570        580        590        600 
GGGVGGAAWR SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI 

       610        620        630        640        650        660 
SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA SGGPSVFQKP 

       670        680        690        700        710        720 
VRFQVDISSS EGPEPSPRRD GSSGGGIYSV TFTLISGPSR RFKRVVETIQ AQLLSTHDQP 

       730        740        750        760        770 
SVQALADEKN GAQTRPAGTP PRSLQPPPGR PDPDLSSSPR RGPSKDKKLL ATNGTPLP 

« Hide

References

« Hide 'large scale' references
[1]"Activation of SAD kinase by Ca2+/calmodulin-dependent protein kinase kinase."
Fujimoto T., Yurimoto S., Hatano N., Nozaki N., Sueyoshi N., Kameshita I., Mizutani A., Mikoshiba K., Kobayashi R., Tokumitsu H.
Biochemistry 47:4151-4159(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-189.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[3]"SAD: a presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release."
Inoue E., Mochida S., Takagi H., Higa S., Deguchi-Tawarada M., Takao-Rikitsu E., Inoue M., Yao I., Takeuchi K., Kitajima I., Setou M., Ohtsuka T., Takai Y.
Neuron 50:261-275(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-63; THR-189 AND SER-193.
[4]"Tuberous sclerosis complex proteins control axon formation."
Choi Y.J., Di Nardo A., Kramvis I., Meikle L., Kwiatkowski D.J., Sahin M., He X.
Genes Dev. 22:2485-2495(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION OF TRANSLATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB365521 mRNA. Translation: BAG28183.1.
RefSeqNP_001120809.1. NM_001127337.1.
UniGeneRn.112844.

3D structure databases

ProteinModelPortalB2DD29.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000033679.

Proteomic databases

PaxDbB2DD29.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000031172; ENSRNOP00000033679; ENSRNOG00000017673.
GeneID499073.
KEGGrno:499073.
UCSCRGD:1563268. rat.

Organism-specific databases

CTD84446.
RGD1563268. Brsk1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000246447.
HOVERGENHBG007240.
KOK08796.
OMAGRHAQYV.
OrthoDBEOG7XSTDH.

Gene expression databases

GenevestigatorB2DD29.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio701750.

Entry information

Entry nameBRSK1_RAT
AccessionPrimary (citable) accession number: B2DD29
Secondary accession number(s): F1M6Y8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 21, 2011
Last sequence update: June 10, 2008
Last modified: March 19, 2014
This is version 44 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families