Q69Z98 (BRSK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
November 13, 2013.
Version 84.
History...
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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 735 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein 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-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. 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 (Ref.9), BRSK2 phosphorylated at Thr-261 can promote insulin secretion (Ref.8). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmatic reticulum (ER) stress. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. Ref.8 ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.8 |
| Cofactor | Magnesium By similarity. |
| Enzyme regulation | Activated by phosphorylation on Thr-175 by STK11/LKB1. |
| Subunit structure | Interacts with FZR1, a regulatory subunit of the APC ubiquitin ligase complex. Interacts with COPS5. Interacts with PAK1 By similarity. Ref.8 |
| Subcellular location | Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm › perinuclear 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. |
| Tissue specificity | Detected in pancreas islets and in brain (at protein level). Detected in brain and pancreas. Ref.9 |
| Domain | The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination 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. Ref.6 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. |
| Disruption phenotype | 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. Ref.1 |
| 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
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q69Z98-1) 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: Q69Z98-2) Also known as: SADA-beta; The sequence of this isoform differs from the canonical sequence as follows: 648-735: DTTNCMEVMT...GPPAARREQP → EPPPPAPGLSWGAGLKGQKVATSYESSL | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: Q69Z98-3) Also known as: SADA-gamma; The sequence of this isoform differs from the canonical sequence as follows: 664-679: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q69Z98-4) Also known as: SADA-alpha; The sequence of this isoform differs from the canonical sequence as follows: 648-653: DTTNCM → GIIPKS 654-735: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 735 | 735 | Serine/threonine-protein kinase BRSK2 | PRO_0000274036 | |||||
Regions | |||||||||
| Domain | 20 – 271 | 252 | Protein kinase | ||||||
| Domain | 298 – 340 | 43 | UBA | ||||||
| Nucleotide binding | 26 – 34 | 9 | ATP By similarity | ||||||
| Motif | 604 – 606 | 3 | KEN box By similarity | ||||||
| Compositional bias | 425 – 469 | 45 | Pro-rich | ||||||
Sites | |||||||||
| Active site | 142 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 49 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 175 | 1 | Phosphothreonine; by LKB1 Ref.6 | ||||||
| Modified residue | 261 | 1 | Phosphothreonine; by PKA By similarity | ||||||
| Modified residue | 368 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 383 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 394 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 413 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 423 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 510 | 1 | Phosphothreonine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 648 – 735 | 88 | DTTNC…RREQP → EPPPPAPGLSWGAGLKGQKV ATSYESSL in isoform 2. | VSP_022605 | |||||
| Alternative sequence | 648 – 653 | 6 | DTTNCM → GIIPKS in isoform 4. | VSP_022607 | |||||
| Alternative sequence | 654 – 735 | 82 | Missing in isoform 4. | VSP_022608 | |||||
| Alternative sequence | 664 – 679 | 16 | Missing in isoform 3. | VSP_022606 | |||||
Experimental info | |||||||||
| Mutagenesis | 49 | 1 | K → A: Loss of kinase activity. Ref.1 | ||||||
| Mutagenesis | 175 | 1 | T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.6 | ||||||
| Sequence conflict | 31 – 43 | 13 | TGLVK…HCVTC → VDGDLLASDTVDS in BAD32546. Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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] (ISOFORMS 2; 3 AND 4), FUNCTION, MUTAGENESIS OF LYS-49, DISRUPTION PHENOTYPE. |
| [2] | Tang W.W., Shan Y.X. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). |
| [3] | "Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.  Ponting C.P.PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J. |
| [4] | "Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H. DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-735 (ISOFORM 1). Tissue: Fetal brain. |
| [5] | "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] OF 131-653 (ISOFORM 4). Strain: C57BL/6. Tissue: Brain. |
| [6] | "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, PHOSPHORYLATION AT THR-175, MUTAGENESIS OF THR-175. |
| [7] | "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. |
| [8] | "Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta-Cells." Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W., Han X., Shi Y. J. Biol. Chem. 287:26435-26444(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PAK1. |
| [9] | "Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic beta-cells." Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L., Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O., Yu L. J. Biol. Chem. 287:30368-30375(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY533672 mRNA. Translation: AAT08447.1. AY533673 mRNA. Translation: AAT08448.1. AY533674 mRNA. Translation: AAT08449.1. AY660739 mRNA. Translation: AAT74618.1. AL603836 Genomic DNA. No translation available. AL772165 Genomic DNA. No translation available. AK173268 mRNA. Translation: BAD32546.1. BC056498 mRNA. Translation: AAH56498.1. |
| IPI | IPI00466901. IPI00551400. IPI00551443. IPI00828329. |
| RefSeq | NP_001009929.1. NM_001009929.3. NP_001009930.1. NM_001009930.3. NP_083702.1. NM_029426.2. |
| UniGene | Mm.274868. Mm.482784. |
3D structure databases | |
| ProteinModelPortal | Q69Z98. |
| SMR | Q69Z98. Positions 16-339. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | 10090.ENSMUSP00000101610. |
PTM databases | |
| PhosphoSite | Q69Z98. |
Proteomic databases | |
| PaxDb | Q69Z98. |
| PRIDE | Q69Z98. |
Protocols and materials databases | |
| DNASU | 75770. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSMUST00000018971; ENSMUSP00000018971; ENSMUSG00000053046. ENSMUST00000075528; ENSMUSP00000074969; ENSMUSG00000053046. ENSMUST00000078200; ENSMUSP00000077330; ENSMUSG00000053046. ENSMUST00000105989; ENSMUSP00000101610; ENSMUSG00000053046. ENSMUST00000174499; ENSMUSP00000134201; ENSMUSG00000053046. |
| GeneID | 75770. |
| KEGG | mmu:75770. |
| UCSC | uc009kme.1. mouse. |
Organism-specific databases | |
| CTD | 9024. |
| MGI | MGI:1923020. Brsk2. |
| Rouge | Search... |
Phylogenomic databases | |
| eggNOG | COG0515. |
| GeneTree | ENSGT00730000110252. |
| HOGENOM | HOG000246447. |
| HOVERGEN | HBG007240. |
| InParanoid | Q69Z98. |
| KO | K08796. |
| OMA | LELPMSQ. |
| OrthoDB | EOG7XSTDH. |
Gene expression databases | |
| ArrayExpress | Q69Z98. |
| Bgee | Q69Z98. |
| CleanEx | MM_BRSK2. |
| Genevestigator | Q69Z98. |
Family and domain databases | |
| InterPro | 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] |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. SSF56112. 2 hits. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 343904. |
| PRO | Q69Z98. |
| SOURCE | Search... |
Entry information
| Entry name | BRSK2_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q69Z98 Secondary accession number(s): Q699J3 Q6PHM0 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |