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Q5RJI5

- BRSK1_MOUSE

UniProt

Q5RJI5 - BRSK1_MOUSE

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
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      Previous versions | rss
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    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 binding Source: MGI
    5. protein kinase binding Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. 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

    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

    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.
    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.
    GeneTreeiENSGT00750000117372.
    HOGENOMiHOG000246447.
    HOVERGENiHBG105719.
    InParanoidiA7LH91.
    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_dom.
    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

    MSSGSKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL    50
    GVHCITGQKV AVKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY 100
    ENKKYLYLVL EHVSGGELFD YLVKKGRLTP KEARKFFRQI VSALDFCHSY 150
    SICHRDLKPE NLLLDEKNNI RIADFGMASL QVGDSLLETS CGSPHYACPE 200
    VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL EKVKRGVFHM 250
    PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP 300
    GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI 350
    YYLLLDRKER YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM 400
    EVLSITDAGS GGSPVPTRRA LEMAQHSQRS RSVSGASTGL SSSPLSSPRS 450
    PVFSFSPEPG AGDEARGGGS PTSKTQTLPS RGPRGGGAGE QPPPPSARST 500
    PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP GGGVGGAAWR 550
    SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI 600
    SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA 650
    SGGPSVFQKP VRFQVDISSS EGPEPSPRRD GSSGGGIYSV TFTLISGPSR 700
    RFKRVVETIQ AQLLSTHDQP SVQALADEKN GAQTRPAGTP PRSLQPPPGR 750
    SDPDLSSSPR RGPPKDKKLL ATNGTPLP 778
    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 ENSGT00750000117372.
    HOGENOMi HOG000246447.
    HOVERGENi HBG105719.
    InParanoidi A7LH91.
    KOi K08796.
    OMAi GRHAQYV.
    PhylomeDBi Q5RJI5.
    TreeFami TF313967.

    Miscellaneous databases

    NextBioi 402808.
    PROi Q5RJI5.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q5RJI5.
    CleanExi MM_BRSK1.
    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_dom.
    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

    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 1, 2014
    This is version 100 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