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D3ZML2 (BRSK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 39. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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 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 names
Name:Brsk2
Synonyms:Sada
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length735 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

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-175 by STK11/LKB1 By similarity.

Subunit structure

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

Subcellular location

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.

Post-translational modification

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.

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.

Miscellaneous

Protein synthesis is inhibited by the TSC1-TSC2 complex acting through TORC1 in neurons, leading to regulate neuron polarization (Ref.3).

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 processApoptosis
Cell cycle
Cell division
Exocytosis
Mitosis
Neurogenesis
   Cellular componentCytoplasm
Cytoskeleton
Endoplasmic reticulum
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2 DNA damage checkpoint

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

establishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

exocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

protein phosphorylation

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

response to UV

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from sequence or structural similarity PubMed 15150265. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: D3ZML2-1)

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: D3ZML2-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 735735Serine/threonine-protein kinase BRSK2
PRO_0000412650

Regions

Domain20 – 271252Protein kinase
Domain298 – 34043UBA
Nucleotide binding26 – 349ATP By similarity
Compositional bias425 – 46945Pro-rich

Sites

Active site1421Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1751Phosphothreonine; by LKB1 By similarity
Modified residue2611Phosphothreonine; by PKA By similarity
Modified residue3681Phosphoserine By similarity
Modified residue3831Phosphoserine By similarity
Modified residue3941Phosphoserine By similarity
Modified residue4131Phosphoserine By similarity
Modified residue4231Phosphothreonine By similarity
Modified residue5101Phosphothreonine By similarity

Natural variations

Alternative sequence4091Q → QSKAVFSKSLDIAEAHPQFS KED in isoform 2.
VSP_041747

Experimental info

Sequence conflict3831S → C in CAJ13860. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 20, 2010. Version 1.
Checksum: F5B7958D753BDB04

FASTA73581,455
        10         20         30         40         50         60 
MTSTGKDGGG AQHAQYVGPY RLEKTLGKGQ TGLVKLGIHC VTCQKVAIKI VNREKLSESV 

        70         80         90        100        110        120 
LMKVEREIAI LKLIEHPHVL KLHDVYENKK YLYLVLEHVS GGELFDYLVK KGRLTPKEAR 

       130        140        150        160        170        180 
KFFRQIISAL DFCHSHSICH RDLKPENLLL DERNNIRIAD FGMASLQVGD SLLETSCGSP 

       190        200        210        220        230        240 
HYACPEVIRG EKYDGRKADV WSCGVILFAL LVGALPFDDD NLRQLLEKVK RGVFHMPHFI 

       250        260        270        280        290        300 
PPDCQSLLRG MIEVDAARRL TLEHIQKHIW YIGGKNEPEP EQPIPRKVQI RSLPSLEDID 

       310        320        330        340        350        360 
PDVLDSMHSL GCFRDRNKLL QDLLSEEENQ EKMIYFLLLD RKERYPSHED EDLPPRNEID 

       370        380        390        400        410        420 
PPRKRVDSPM LNRHGKRRPE RKSMEVLSVT DGGSPVPARR AIEMAQHGQR SRSISGASSG 

       430        440        450        460        470        480 
LSTSPLSSPR VTPHPSPRGS PLPTPKGTPV HTPKESPAGT PNPTPPSSPS VGGVPWRTRL 

       490        500        510        520        530        540 
NSIKNSFLGS PRFHRRKLQV PTPEEMSNLT PESSPELGHL QLFGNPVSKV RSVAMELVIL 

       550        560        570        580        590        600 
VQTLAYTSFR LLGTFLPVRY LRHSVLSRPP ERARLVLRGA PCTHMGPVWN MVGMAYTQNP 

       610        620        630        640        650        660 
PIMGETGVYG SQWVMSSAPS KHYTSLGLSV PSPSCSLSPS LFPFCAPDTT NCMEVMTGRL 

       670        680        690        700        710        720 
SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG PLGDSAAAGP GGDTEYPMGK 

       730 
DMAKMGPPAA RREQP 

« Hide

Isoform 2 [UniParc].

Checksum: CE64C66E6C6797C1
Show »

FASTA75783,871

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AM040976 mRNA. Translation: CAJ13860.1.
UniGeneRn.232994.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000027134.

PTM databases

PhosphoSiteD3ZML2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

RGD1566256. Brsk2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000246447.
HOVERGENHBG105719.
PhylomeDBD3ZML2.
TreeFamTF313967.

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.
[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.
[Graphical view]
ProtoNetSearch...

Other

PROD3ZML2.

Entry information

Entry nameBRSK2_RAT
AccessionPrimary (citable) accession number: D3ZML2
Secondary accession number(s): E9PTC7, Q4A1P4
Entry history
Integrated into UniProtKB/Swiss-Prot: September 21, 2011
Last sequence update: April 20, 2010
Last modified: April 16, 2014
This is version 39 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