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Q5RJI5

- BRSK1_MOUSE

UniProt

Q5RJI5 - BRSK1_MOUSE

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Protein

Serine/threonine-protein kinase BRSK1

Gene

Brsk1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Magnesium.By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei63 – 631ATPCurated
Active sitei156 – 1561Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi40 – 489ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. gamma-tubulin binding Source: UniProtKB
  3. magnesium ion binding Source: UniProtKB
  4. protein kinase binding Source: UniProtKB
  5. protein serine/threonine kinase activity Source: UniProtKB
  6. tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  1. axonogenesis Source: UniProtKB
  2. cellular response to DNA damage stimulus Source: UniProtKB
  3. centrosome duplication Source: UniProtKB
  4. establishment of cell polarity Source: UniProtKB
  5. G2 DNA damage checkpoint Source: UniProtKB
  6. neuron differentiation Source: MGI
  7. neuron projection morphogenesis Source: MGI
  8. neurotransmitter secretion Source: UniProtKB
  9. protein phosphorylation Source: UniProtKB
  10. 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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:2685946. Brsk1.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. centrosome Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. nucleus Source: UniProtKB
  5. plasma membrane Source: Ensembl
  6. 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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi63 – 631K → R: Abolishes kinase activity and ability to regulate centrosome duplication. 1 Publication
Mutagenesisi189 – 1891T → A: Abolishes activation by STK11/LKB1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 778778Serine/threonine-protein kinase BRSK1PRO_0000260829Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei189 – 1891Phosphothreonine; by LKB11 Publication
Modified residuei447 – 4471PhosphoserineBy similarity
Modified residuei508 – 5081PhosphoserineBy similarity
Modified residuei563 – 5631PhosphoserineBy similarity

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

Phosphoprotein

Proteomic databases

MaxQBiQ5RJI5.
PaxDbiQ5RJI5.
PRIDEiQ5RJI5.

PTM databases

PhosphoSiteiQ5RJI5.

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

BgeeiQ5RJI5.
CleanExiMM_BRSK1.
ExpressionAtlasiQ5RJI5. baseline.
GenevestigatoriQ5RJI5.

Interactioni

Protein-protein interaction databases

BioGridi238175. 2 interactions.
IntActiQ5RJI5. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ5RJI5.
SMRiQ5RJI5. Positions 30-355.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 285252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini314 – 35643UBAPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi492 – 54049Pro-richAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119244.
HOGENOMiHOG000246447.
HOVERGENiHBG105719.
InParanoidiQ5RJI5.
KOiK08796.
OMAiGRHAQYV.
PhylomeDBiQ5RJI5.
TreeFamiTF313967.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

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 3 (identifier: Q5RJI5-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-19: Missing.
     344-778: Missing.

Show »
Length:341
Mass (Da):38,550
Checksum:i4325DB8A403F61C9
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 242Missing in AAT08446. (PubMed:15705853)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4545MSSGS…GKGQT → MQKFGIEEM in isoform 4. 1 PublicationVSP_041743Add
BLAST
Alternative sequencei18 – 192Missing in isoform 3. 1 PublicationVSP_041744
Alternative sequencei344 – 778435Missing in isoform 2, isoform 3 and isoform 4. 1 PublicationVSP_041745Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS20741.1. [Q5RJI5-1 ]
RefSeqi NP_001003920.2. NM_001003920.3. [Q5RJI5-1 ]
NP_001162044.1. NM_001168572.1. [Q5RJI5-2 ]
UniGenei Mm.297064.

3D structure databases

ProteinModelPortali Q5RJI5.
SMRi Q5RJI5. Positions 30-355.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 238175. 2 interactions.
IntActi Q5RJI5. 2 interactions.

PTM databases

PhosphoSitei Q5RJI5.

Proteomic databases

MaxQBi Q5RJI5.
PaxDbi Q5RJI5.
PRIDEi Q5RJI5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000048248 ; ENSMUSP00000039517 ; ENSMUSG00000035390 . [Q5RJI5-1 ]
GeneIDi 381979.
KEGGi mmu:381979.
UCSCi uc009eye.2. mouse. [Q5RJI5-2 ]
uc009eyf.1. mouse. [Q5RJI5-1 ]

Organism-specific databases

CTDi 84446.
MGIi MGI:2685946. Brsk1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119244.
HOGENOMi HOG000246447.
HOVERGENi HBG105719.
InParanoidi Q5RJI5.
KOi K08796.
OMAi GRHAQYV.
PhylomeDBi Q5RJI5.
TreeFami TF313967.

Miscellaneous databases

NextBioi 402808.
PROi Q5RJI5.
SOURCEi Search...

Gene expression databases

Bgeei Q5RJI5.
CleanExi MM_BRSK1.
ExpressionAtlasi Q5RJI5. baseline.
Genevestigatori Q5RJI5.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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: October 29, 2014
This is version 101 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

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3