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Q5RJI5 (BRSK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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:Gm1100, Sadb
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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-504' and 'Ser-554'. 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. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. 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. Ref.1 Ref.2 Ref.4 Ref.5

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. Ref.4

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cell junctionsynapse By similarity. Note: Nuclear in the absence of DNA damage. Translocated to the nucleus in response to UV- or MMS-induced DNA damage. Localizes to synaptic vesicles in neurons By similarity. Ref.2

Tissue specificity

Present in the gray matter of the brain and spinal cord (at protein level). Expressed in the nervous system, distributed within the brain and spinal cord of embryonic and postnatal animals. Ref.1

Developmental stage

Activity is high in G0, decreases after serum addition, and increases transiently in advanced G1, at G1-S, and in S phases. Ref.2

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. Ref.4

Disruption phenotype

No visible phenotype. Mice are fertile and healthy. In contrast, mice lacking both Brsk1 and Brsk2 show little spontaneous movement and are only weakly responsive to tactile stimulation: they die within 2 hours of birth. Defects are due to impaired neuronal differentiation and polarity. Ref.1

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
   Coding sequence diversityAlternative splicing
   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 sequence or structural similarity. Source: UniProtKB

axonogenesis

Inferred from mutant phenotype Ref.4. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome duplication

Inferred from mutant phenotype Ref.2. Source: UniProtKB

establishment of cell polarity

Inferred from mutant phenotype Ref.4. Source: UniProtKB

neuron differentiation

Inferred from genetic interaction Ref.1. Source: MGI

neuron projection morphogenesis

Inferred from genetic interaction Ref.5. Source: MGI

neurotransmitter secretion

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

response to UV

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

centrosome

Inferred from direct assay Ref.2. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

gamma-tubulin binding

Inferred from direct assay Ref.2. Source: UniProtKB

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5. Source: MGI

protein kinase binding

Inferred from physical interaction Ref.4. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

tau-protein kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5RJI5-1)

Also known as: SADB-Long; L;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q5RJI5-2)

Also known as: SADB-short; S;

The sequence of this isoform differs from the canonical sequence as follows:
     344-778: Missing.
Isoform 3 (identifier: Q5RJI5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     18-19: Missing.
     344-778: Missing.
Isoform 4 (identifier: Q5RJI5-4)

Also known as: SADB-short 1; S1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: MSSGSKEGGGGSPAYHLPHPHPHPPQHAQYVGPYRLEKTLGKGQT → MQKFGIEEM
     344-778: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 778778Serine/threonine-protein kinase BRSK1
PRO_0000260829

Regions

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

Sites

Active site1561Proton acceptor By similarity
Binding site631ATP Probable

Amino acid modifications

Modified residue1891Phosphothreonine; by LKB1 Ref.4
Modified residue4471Phosphoserine By similarity
Modified residue5081Phosphoserine By similarity
Modified residue5631Phosphoserine By similarity

Natural variations

Alternative sequence1 – 4545MSSGS…GKGQT → MQKFGIEEM in isoform 4.
VSP_041743
Alternative sequence18 – 192Missing in isoform 3.
VSP_041744
Alternative sequence344 – 778435Missing in isoform 2, isoform 3 and isoform 4.
VSP_041745

Experimental info

Mutagenesis631K → R: Abolishes kinase activity and ability to regulate centrosome duplication. Ref.2
Mutagenesis1891T → A: Abolishes activation by STK11/LKB1. Ref.4
Sequence conflict23 – 242Missing in AAT08446. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (SADB-Long) (L) [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: A35C86293A958D99

FASTA77885,155
        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 AGDEARGGGS 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 SDPDLSSSPR RGPPKDKKLL ATNGTPLP 

« Hide

Isoform 2 (SADB-short) (S) [UniParc].

Checksum: 68E7641FE96C78ED
Show »

FASTA34338,784
Isoform 3 [UniParc].

Checksum: 4325DB8A403F61C9
Show »

FASTA34138,550
Isoform 4 (SADB-short 1) (S1) [UniParc].

Checksum: BE47903FBDE6F9C6
Show »

FASTA30735,121

References

« Hide 'large scale' references
[1]"Mammalian SAD kinases are required for neuronal polarization."
Kishi M., Pan Y.A., Crump J.G., Sanes J.R.
Science 307:929-932(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[2]"SADB phosphorylation of gamma-tubulin regulates centrosome duplication."
Alvarado-Kristensson M., Rodriguez M.J., Silio V., Valpuesta J.M., Carrera A.C.
Nat. Cell Biol. 11:1081-1092(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-63, DEVELOPMENTAL STAGE.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
[4]"LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons."
Barnes A.P., Lilley B.N., Pan Y.A., Plummer L.J., Powell A.W., Raines A.N., Sanes J.R., Polleux F.
Cell 129:549-563(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-189, MUTAGENESIS OF THR-189.
[5]"Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity."
Muller M., Lutter D., Puschel A.W.
J. Cell Sci. 123:286-294(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY533671 mRNA. Translation: AAT08446.1.
EU586326 mRNA. Translation: ACE82255.1.
EU016556 mRNA. Translation: ABS57358.1.
EU016557 mRNA. Translation: ABS57359.1.
EU016558 mRNA. Translation: ABS57360.1.
BC086636 mRNA. Translation: AAH86636.1.
CCDSCCDS20741.1. [Q5RJI5-1]
RefSeqNP_001003920.2. NM_001003920.3. [Q5RJI5-1]
NP_001162044.1. NM_001168572.1. [Q5RJI5-2]
UniGeneMm.297064.

3D structure databases

ProteinModelPortalQ5RJI5.
SMRQ5RJI5. Positions 30-355.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid238175. 2 interactions.
IntActQ5RJI5. 2 interactions.

PTM databases

PhosphoSiteQ5RJI5.

Proteomic databases

MaxQBQ5RJI5.
PaxDbQ5RJI5.
PRIDEQ5RJI5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000048248; ENSMUSP00000039517; ENSMUSG00000035390. [Q5RJI5-1]
GeneID381979.
KEGGmmu:381979.
UCSCuc009eye.2. mouse. [Q5RJI5-2]
uc009eyf.1. mouse. [Q5RJI5-1]

Organism-specific databases

CTD84446.
MGIMGI:2685946. Brsk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117372.
HOGENOMHOG000246447.
HOVERGENHBG105719.
InParanoidA7LH91.
KOK08796.
OMAGRHAQYV.
PhylomeDBQ5RJI5.
TreeFamTF313967.

Gene expression databases

BgeeQ5RJI5.
CleanExMM_BRSK1.
GenevestigatorQ5RJI5.

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

NextBio402808.
PROQ5RJI5.
SOURCESearch...

Entry information

Entry nameBRSK1_MOUSE
AccessionPrimary (citable) accession number: Q5RJI5
Secondary accession number(s): A7LH90 expand/collapse secondary AC list , A7LH91, B7SRN7, Q699J6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: December 21, 2004
Last modified: July 9, 2014
This is version 99 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot