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D3ZML2

- BRSK2_RAT

UniProt

D3ZML2 - BRSK2_RAT

Protein

Serine/threonine-protein kinase BRSK2

Gene

Brsk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 41 (01 Oct 2014)
      Sequence version 1 (20 Apr 2010)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 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. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-175 can inhibit insulin secretion, BRSK2 phosphorylated at Thr-261 can promote insulin secretion. Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmatic reticulum (ER) stress By similarity.By similarity

    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-175 by STK11/LKB1.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei49 – 491ATPPROSITE-ProRule annotation
    Active sitei142 – 1421Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. protein serine/threonine kinase activity Source: UniProtKB
    4. tau-protein kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. axonogenesis Source: UniProtKB
    3. cellular response to DNA damage stimulus Source: UniProtKB
    4. establishment of cell polarity Source: UniProtKB
    5. exocytosis Source: UniProtKB-KW
    6. G2 DNA damage checkpoint Source: UniProtKB
    7. mitotic nuclear division Source: UniProtKB-KW
    8. protein phosphorylation Source: UniProtKB
    9. response to UV Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle, Cell division, Exocytosis, Mitosis, Neurogenesis

    Keywords - Ligandi

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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase BRSK2 (EC:2.7.11.1, EC:2.7.11.26)
    Alternative name(s):
    Brain-specific serine/threonine-protein kinase 2
    Short name:
    BR serine/threonine-protein kinase 2
    Serine/threonine-protein kinase SAD-A
    Gene namesi
    Name:Brsk2
    Synonyms:Sada
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi1566256. Brsk2.

    Subcellular locationi

    Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmperinuclear region By similarity. Endoplasmic reticulum By similarity
    Note: Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum Source: UniProtKB-SubCell
    3. microtubule organizing center Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB
    5. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Endoplasmic reticulum

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 735735Serine/threonine-protein kinase BRSK2PRO_0000412650Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei175 – 1751Phosphothreonine; by LKB1By similarity
    Modified residuei261 – 2611Phosphothreonine; by PKABy similarity
    Modified residuei368 – 3681PhosphoserineBy similarity
    Modified residuei383 – 3831PhosphoserineBy similarity
    Modified residuei394 – 3941PhosphoserineBy similarity
    Modified residuei413 – 4131PhosphoserineBy similarity
    Modified residuei423 – 4231PhosphothreonineBy similarity
    Modified residuei510 – 5101PhosphothreonineBy similarity

    Post-translational modificationi

    May be phosphorylated at Thr-261 by PKA By similarity. Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-175 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-175 by PP2C By similarity.By similarity
    Polyubiquitinated by the APC complex in conjunction with FZR1, leading to its proteasomal degradation. Targeted for proteasomal degradation by interaction with COPS5. BRSK2 levels change during the cell cycle. BRSK2 levels are low at the G1/S boundary and gradually increase as cells progress into G2 phase. BRSK2 levels decrease rapidly at the end of mitosis By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    PTM databases

    PhosphoSiteiD3ZML2.

    Interactioni

    Subunit structurei

    Interacts with FZR1, a regulatory subunit of the APC ubiquitin ligase complex. Interacts with COPS5. Interacts with PAK1 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000027134.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini20 – 271252Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini298 – 34043UBAAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi425 – 46945Pro-richAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000246447.
    HOVERGENiHBG105719.
    PhylomeDBiD3ZML2.
    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.
    [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.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: D3ZML2-1) [UniParc]FASTAAdd to Basket

    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

    MTSTGKDGGG AQHAQYVGPY RLEKTLGKGQ TGLVKLGIHC VTCQKVAIKI    50
    VNREKLSESV LMKVEREIAI LKLIEHPHVL KLHDVYENKK YLYLVLEHVS 100
    GGELFDYLVK KGRLTPKEAR KFFRQIISAL DFCHSHSICH RDLKPENLLL 150
    DERNNIRIAD FGMASLQVGD SLLETSCGSP HYACPEVIRG EKYDGRKADV 200
    WSCGVILFAL LVGALPFDDD NLRQLLEKVK RGVFHMPHFI PPDCQSLLRG 250
    MIEVDAARRL TLEHIQKHIW YIGGKNEPEP EQPIPRKVQI RSLPSLEDID 300
    PDVLDSMHSL GCFRDRNKLL QDLLSEEENQ EKMIYFLLLD RKERYPSHED 350
    EDLPPRNEID PPRKRVDSPM LNRHGKRRPE RKSMEVLSVT DGGSPVPARR 400
    AIEMAQHGQR SRSISGASSG LSTSPLSSPR VTPHPSPRGS PLPTPKGTPV 450
    HTPKESPAGT PNPTPPSSPS VGGVPWRTRL NSIKNSFLGS PRFHRRKLQV 500
    PTPEEMSNLT PESSPELGHL QLFGNPVSKV RSVAMELVIL VQTLAYTSFR 550
    LLGTFLPVRY LRHSVLSRPP ERARLVLRGA PCTHMGPVWN MVGMAYTQNP 600
    PIMGETGVYG SQWVMSSAPS KHYTSLGLSV PSPSCSLSPS LFPFCAPDTT 650
    NCMEVMTGRL SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG 700
    PLGDSAAAGP GGDTEYPMGK DMAKMGPPAA RREQP 735
    Length:735
    Mass (Da):81,455
    Last modified:April 20, 2010 - v1
    Checksum:iF5B7958D753BDB04
    GO
    Isoform 2 (identifier: D3ZML2-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         409-409: Q → QSKAVFSKSLDIAEAHPQFSKED

    Show »
    Length:757
    Mass (Da):83,871
    Checksum:iCE64C66E6C6797C1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti383 – 3831S → C in CAJ13860. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei409 – 4091Q → QSKAVFSKSLDIAEAHPQFS KED in isoform 2. 1 PublicationVSP_041747

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AM040976 mRNA. Translation: CAJ13860.1.
    UniGeneiRn.232994.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AM040976 mRNA. Translation: CAJ13860.1 .
    UniGenei Rn.232994.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000027134.

    PTM databases

    PhosphoSitei D3ZML2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    RGDi 1566256. Brsk2.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000246447.
    HOVERGENi HBG105719.
    PhylomeDBi D3ZML2.
    TreeFami TF313967.

    Miscellaneous databases

    PROi D3ZML2.

    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.
    [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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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.
      , 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.
    2. "BR serine/threonine Kinase 2: a new autoantigen in paraneoplastic limbic encephalitis."
      Sabater L., Gomez-Choco M., Saiz A., Graus F.
      Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-457 (ISOFORM 2).
      Strain: Sprague-Dawley.
      Tissue: Hippocampus.
    3. "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.

    Entry informationi

    Entry nameiBRSK2_RAT
    AccessioniPrimary (citable) accession number: D3ZML2
    Secondary accession number(s): E9PTC7, Q4A1P4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 21, 2011
    Last sequence update: April 20, 2010
    Last modified: October 1, 2014
    This is version 41 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Protein synthesis is inhibited by the TSC1-TSC2 complex acting through TORC1 in neurons, leading to regulate neuron polarization.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3