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Protein

Serine/threonine-protein kinase BRSK1

Gene

Brsk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

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

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation on Thr-189 by STK11/LKB1.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei63ATPCurated1
Active sitei156Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 48ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • gamma-tubulin binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  • axonogenesis Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • centrosome duplication Source: UniProtKB
  • establishment of cell polarity Source: UniProtKB
  • G2/M transition of mitotic cell cycle Source: MGI
  • G2 DNA damage checkpoint Source: UniProtKB
  • intracellular signal transduction Source: GO_Central
  • neuron differentiation Source: MGI
  • neuron projection morphogenesis Source: MGI
  • neurotransmitter secretion Source: UniProtKB
  • peptidyl-serine phosphorylation Source: MGI
  • protein phosphorylation Source: UniProtKB
  • response to UV Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, DNA damage, Neurogenesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Brsk1
Synonyms:Gm1100, Sadb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2685946. Brsk1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: MGI
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • synaptic vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoskeleton, Nucleus, Synapse

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63K → R: Abolishes kinase activity and ability to regulate centrosome duplication. 1 Publication1
Mutagenesisi189T → A: Abolishes activation by STK11/LKB1. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002608291 – 778Serine/threonine-protein kinase BRSK1Add BLAST778

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei189Phosphothreonine; by LKB11 Publication1
Modified residuei399PhosphoserineCombined sources1
Modified residuei443PhosphoserineCombined sources1
Modified residuei447PhosphoserineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei466Omega-N-methylarginineCombined sources1
Modified residuei481Omega-N-methylarginineCombined sources1
Modified residuei484Omega-N-methylarginineCombined sources1
Modified residuei498Omega-N-methylarginineCombined sources1
Modified residuei508PhosphoserineBy similarity1
Modified residuei525Omega-N-methylarginineCombined sources1
Modified residuei529PhosphothreonineCombined sources1
Modified residuei535PhosphothreonineCombined sources1
Modified residuei550Omega-N-methylarginineCombined sources1
Modified residuei563PhosphoserineBy similarity1
Modified residuei583PhosphothreonineCombined sources1
Modified residuei586PhosphoserineBy similarity1
Modified residuei587PhosphoserineBy similarity1
Modified residuei601PhosphoserineBy similarity1

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ5RJI5.
PeptideAtlasiQ5RJI5.
PRIDEiQ5RJI5.

PTM databases

iPTMnetiQ5RJI5.
PhosphoSitePlusiQ5RJI5.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

Activity is high in G0, decreases after serum addition, and increases transiently in advanced G1, at G1-S, and in S phases.1 Publication

Gene expression databases

BgeeiENSMUSG00000035390.
CleanExiMM_BRSK1.
ExpressionAtlasiQ5RJI5. baseline and differential.
GenevisibleiQ5RJI5. MM.

Interactioni

GO - Molecular functioni

  • gamma-tubulin binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi238175. 2 interactors.
IntActiQ5RJI5. 3 interactors.
STRINGi10090.ENSMUSP00000039517.

Structurei

Secondary structure

1778
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi598 – 602Combined sources5
Beta strandi605 – 614Combined sources10
Helixi617 – 630Combined sources14
Beta strandi634 – 640Combined sources7
Beta strandi643 – 648Combined sources6
Helixi649 – 651Combined sources3
Beta strandi654 – 658Combined sources5
Beta strandi661 – 669Combined sources9
Beta strandi688 – 697Combined sources10
Helixi699 – 714Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IRIX-ray2.80A/B592-719[»]
ProteinModelPortaliQ5RJI5.
SMRiQ5RJI5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 285Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini314 – 356UBAPROSITE-ProRule annotationAdd BLAST43

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi492 – 540Pro-richAdd BLAST49

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOGENOMiHOG000246447.
HOVERGENiHBG105719.
InParanoidiQ5RJI5.
KOiK08796.
OMAiGRHAQYV.
OrthoDBiEOG091G02CG.
PhylomeDBiQ5RJI5.
TreeFamiTF313967.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5RJI5-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSSGSKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL
60 70 80 90 100
GVHCITGQKV AVKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY
110 120 130 140 150
ENKKYLYLVL EHVSGGELFD YLVKKGRLTP KEARKFFRQI VSALDFCHSY
160 170 180 190 200
SICHRDLKPE NLLLDEKNNI RIADFGMASL QVGDSLLETS CGSPHYACPE
210 220 230 240 250
VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL EKVKRGVFHM
260 270 280 290 300
PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP
310 320 330 340 350
GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI
360 370 380 390 400
YYLLLDRKER YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM
410 420 430 440 450
EVLSITDAGS GGSPVPTRRA LEMAQHSQRS RSVSGASTGL SSSPLSSPRS
460 470 480 490 500
PVFSFSPEPG AGDEARGGGS PTSKTQTLPS RGPRGGGAGE QPPPPSARST
510 520 530 540 550
PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP GGGVGGAAWR
560 570 580 590 600
SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI
610 620 630 640 650
SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA
660 670 680 690 700
SGGPSVFQKP VRFQVDISSS EGPEPSPRRD GSSGGGIYSV TFTLISGPSR
710 720 730 740 750
RFKRVVETIQ AQLLSTHDQP SVQALADEKN GAQTRPAGTP PRSLQPPPGR
760 770
SDPDLSSSPR RGPPKDKKLL ATNGTPLP
Length:778
Mass (Da):85,155
Last modified:December 21, 2004 - v1
Checksum:iA35C86293A958D99
GO
Isoform 2 (identifier: Q5RJI5-2) [UniParc]FASTAAdd to basket
Also known as: SADB-short, S

The sequence of this isoform differs from the canonical sequence as follows:
     344-778: Missing.

Show »
Length:343
Mass (Da):38,784
Checksum:i68E7641FE96C78ED
GO
Isoform 4 (identifier: Q5RJI5-4) [UniParc]FASTAAdd to basket
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.

Show »
Length:307
Mass (Da):35,121
Checksum:iBE47903FBDE6F9C6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18 – 19Missing in ABS57359 (PubMed:19648910).Curated2
Sequence conflicti18 – 19Missing in ABS57360 (PubMed:19648910).Curated2
Sequence conflicti23 – 24Missing in AAT08446 (PubMed:15705853).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0417431 – 45MSSGS…GKGQT → MQKFGIEEM in isoform 4. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_041745344 – 778Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST435

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS20741.1. [Q5RJI5-1]
RefSeqiNP_001003920.2. NM_001003920.3. [Q5RJI5-1]
NP_001162044.1. NM_001168572.1. [Q5RJI5-2]
UniGeneiMm.297064.

Genome annotation databases

EnsembliENSMUST00000048248; ENSMUSP00000039517; ENSMUSG00000035390. [Q5RJI5-1]
ENSMUST00000205666; ENSMUSP00000145845; ENSMUSG00000035390. [Q5RJI5-4]
ENSMUST00000206024; ENSMUSP00000145970; ENSMUSG00000035390. [Q5RJI5-2]
GeneIDi381979.
KEGGimmu:381979.
UCSCiuc009eye.2. mouse. [Q5RJI5-2]
uc009eyf.1. mouse. [Q5RJI5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS20741.1. [Q5RJI5-1]
RefSeqiNP_001003920.2. NM_001003920.3. [Q5RJI5-1]
NP_001162044.1. NM_001168572.1. [Q5RJI5-2]
UniGeneiMm.297064.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IRIX-ray2.80A/B592-719[»]
ProteinModelPortaliQ5RJI5.
SMRiQ5RJI5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi238175. 2 interactors.
IntActiQ5RJI5. 3 interactors.
STRINGi10090.ENSMUSP00000039517.

PTM databases

iPTMnetiQ5RJI5.
PhosphoSitePlusiQ5RJI5.

Proteomic databases

PaxDbiQ5RJI5.
PeptideAtlasiQ5RJI5.
PRIDEiQ5RJI5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048248; ENSMUSP00000039517; ENSMUSG00000035390. [Q5RJI5-1]
ENSMUST00000205666; ENSMUSP00000145845; ENSMUSG00000035390. [Q5RJI5-4]
ENSMUST00000206024; ENSMUSP00000145970; ENSMUSG00000035390. [Q5RJI5-2]
GeneIDi381979.
KEGGimmu:381979.
UCSCiuc009eye.2. mouse. [Q5RJI5-2]
uc009eyf.1. mouse. [Q5RJI5-1]

Organism-specific databases

CTDi84446.
MGIiMGI:2685946. Brsk1.

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOGENOMiHOG000246447.
HOVERGENiHBG105719.
InParanoidiQ5RJI5.
KOiK08796.
OMAiGRHAQYV.
OrthoDBiEOG091G02CG.
PhylomeDBiQ5RJI5.
TreeFamiTF313967.

Miscellaneous databases

PROiQ5RJI5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035390.
CleanExiMM_BRSK1.
ExpressionAtlasiQ5RJI5. baseline and differential.
GenevisibleiQ5RJI5. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBRSK1_MOUSE
AccessioniPrimary (citable) accession number: Q5RJI5
Secondary accession number(s): A7LH90
, A7LH91, B7SRN7, Q699J6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: December 21, 2004
Last modified: November 30, 2016
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.