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D3ZML2

- BRSK2_RAT

UniProt

D3ZML2 - BRSK2_RAT

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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

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

Mg2+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
Complete GO annotation...

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. cytoskeleton Source: UniProtKB-KW
  3. endoplasmic reticulum Source: UniProtKB-KW
  4. nucleus Source: UniProtKB
Complete GO annotation...

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.
InParanoidiD3ZML2.
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.
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

        10         20         30         40         50
MTSTGKDGGG AQHAQYVGPY RLEKTLGKGQ TGLVKLGIHC VTCQKVAIKI
60 70 80 90 100
VNREKLSESV LMKVEREIAI LKLIEHPHVL KLHDVYENKK YLYLVLEHVS
110 120 130 140 150
GGELFDYLVK KGRLTPKEAR KFFRQIISAL DFCHSHSICH RDLKPENLLL
160 170 180 190 200
DERNNIRIAD FGMASLQVGD SLLETSCGSP HYACPEVIRG EKYDGRKADV
210 220 230 240 250
WSCGVILFAL LVGALPFDDD NLRQLLEKVK RGVFHMPHFI PPDCQSLLRG
260 270 280 290 300
MIEVDAARRL TLEHIQKHIW YIGGKNEPEP EQPIPRKVQI RSLPSLEDID
310 320 330 340 350
PDVLDSMHSL GCFRDRNKLL QDLLSEEENQ EKMIYFLLLD RKERYPSHED
360 370 380 390 400
EDLPPRNEID PPRKRVDSPM LNRHGKRRPE RKSMEVLSVT DGGSPVPARR
410 420 430 440 450
AIEMAQHGQR SRSISGASSG LSTSPLSSPR VTPHPSPRGS PLPTPKGTPV
460 470 480 490 500
HTPKESPAGT PNPTPPSSPS VGGVPWRTRL NSIKNSFLGS PRFHRRKLQV
510 520 530 540 550
PTPEEMSNLT PESSPELGHL QLFGNPVSKV RSVAMELVIL VQTLAYTSFR
560 570 580 590 600
LLGTFLPVRY LRHSVLSRPP ERARLVLRGA PCTHMGPVWN MVGMAYTQNP
610 620 630 640 650
PIMGETGVYG SQWVMSSAPS KHYTSLGLSV PSPSCSLSPS LFPFCAPDTT
660 670 680 690 700
NCMEVMTGRL SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG
710 720 730
PLGDSAAAGP GGDTEYPMGK DMAKMGPPAA RREQP
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:
EMBLi
GenBanki
DDBJi
Links Updated
AM040976 mRNA. Translation: CAJ13860.1.
UniGeneiRn.232994.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
InParanoidi D3ZML2.
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.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 43 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