UniProtKB - Q69Z98 (BRSK2_MOUSE)
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Protein
Serine/threonine-protein kinase BRSK2
Gene
Brsk2
Organism
Mus musculus (Mouse)
Status
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-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 (PubMed:22798068), BRSK2 phosphorylated at Thr-261 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress.5 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.1 Publication
ATP + [tau protein] = ADP + [tau protein] phosphate.1 Publication
Cofactori
Mg2+By similarity
Enzyme regulationi
Activated by phosphorylation on Thr-175 by STK11/LKB1.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 49 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 142 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 26 – 34 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATPase binding Source: MGI
- ATP binding Source: MGI
- magnesium ion binding Source: MGI
- protein kinase binding Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB
- tau-protein kinase activity Source: UniProtKB
GO - Biological processi
- actin cytoskeleton reorganization Source: MGI
- axonogenesis Source: UniProtKB
- cell division Source: UniProtKB-KW
- ERAD pathway Source: MGI
- establishment of cell polarity Source: UniProtKB
- exocytosis Source: UniProtKB-KW
- G2/M transition of mitotic cell cycle Source: MGI
- intracellular signal transduction Source: GO_Central
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGI
- neuron differentiation Source: UniProtKB
- neuron projection morphogenesis Source: MGI
- peptidyl-serine phosphorylation Source: MGI
- protein phosphorylation Source: UniProtKB
- regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Cell cycle, Cell division, Exocytosis, Mitosis, Neurogenesis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Brsk2 Synonyms:Kiaa4256, Sada |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1923020. Brsk2. |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 49 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 175 | T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000274036 | 1 – 735 | Serine/threonine-protein kinase BRSK2Add BLAST | 735 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 175 | Phosphothreonine; by LKB11 Publication | 1 | |
Modified residuei | 261 | Phosphothreonine; by PKABy similarity | 1 | |
Modified residuei | 295 | PhosphoserineBy similarity | 1 | |
Modified residuei | 368 | PhosphoserineBy similarity | 1 | |
Modified residuei | 383 | PhosphoserineCombined sources | 1 | |
Modified residuei | 394 | PhosphoserineCombined sources | 1 | |
Modified residuei | 413 | PhosphoserineCombined sources | 1 | |
Modified residuei | 424 | PhosphoserineCombined sources | 1 | |
Modified residuei | 428 | PhosphoserineCombined sources | 1 | |
Modified residuei | 456 | PhosphoserineCombined sources | 1 | |
Modified residuei | 460 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 464 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 510 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 513 | PhosphoserineCombined sources | 1 | |
Modified residuei | 514 | PhosphoserineCombined sources | 1 | |
Modified residuei | 521 | PhosphoserineCombined sources | 1 |
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 similarity1 Publication
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 conjugationProteomic databases
PaxDbi | Q69Z98. |
PeptideAtlasi | Q69Z98. |
PRIDEi | Q69Z98. |
PTM databases
iPTMneti | Q69Z98. |
PhosphoSitePlusi | Q69Z98. |
Expressioni
Tissue specificityi
Detected in pancreas islets and in brain (at protein level). Detected in brain and pancreas.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000053046. |
CleanExi | MM_BRSK2. |
ExpressionAtlasi | Q69Z98. baseline and differential. |
Genevisiblei | Q69Z98. MM. |
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
GO - Molecular functioni
- ATPase binding Source: MGI
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 217728. 1 interactor. |
STRINGi | 10090.ENSMUSP00000074969. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 15 – 17 | Combined sources | 3 | |
Beta strandi | 20 – 29 | Combined sources | 10 | |
Beta strandi | 32 – 39 | Combined sources | 8 | |
Turni | 40 – 42 | Combined sources | 3 | |
Beta strandi | 45 – 53 | Combined sources | 9 | |
Helixi | 58 – 71 | Combined sources | 14 | |
Beta strandi | 82 – 87 | Combined sources | 6 | |
Beta strandi | 89 – 96 | Combined sources | 8 | |
Helixi | 104 – 111 | Combined sources | 8 | |
Helixi | 116 – 135 | Combined sources | 20 | |
Helixi | 145 – 147 | Combined sources | 3 | |
Beta strandi | 148 – 150 | Combined sources | 3 | |
Beta strandi | 156 – 158 | Combined sources | 3 | |
Helixi | 164 – 166 | Combined sources | 3 | |
Beta strandi | 172 – 174 | Combined sources | 3 | |
Helixi | 180 – 182 | Combined sources | 3 | |
Helixi | 185 – 188 | Combined sources | 4 | |
Helixi | 195 – 212 | Combined sources | 18 | |
Helixi | 222 – 231 | Combined sources | 10 | |
Helixi | 242 – 251 | Combined sources | 10 | |
Turni | 256 – 258 | Combined sources | 3 | |
Helixi | 262 – 266 | Combined sources | 5 | |
Helixi | 269 – 272 | Combined sources | 4 | |
Turni | 274 – 276 | Combined sources | 3 | |
Helixi | 296 – 298 | Combined sources | 3 | |
Helixi | 301 – 308 | Combined sources | 8 | |
Helixi | 311 – 313 | Combined sources | 3 | |
Helixi | 316 – 324 | Combined sources | 9 | |
Beta strandi | 325 – 327 | Combined sources | 3 | |
Helixi | 330 – 342 | Combined sources | 13 | |
Beta strandi | 520 – 523 | Combined sources | 4 | |
Turni | 524 – 526 | Combined sources | 3 | |
Beta strandi | 530 – 532 | Combined sources | 3 | |
Beta strandi | 534 – 539 | Combined sources | 6 | |
Helixi | 544 – 556 | Combined sources | 13 | |
Beta strandi | 561 – 567 | Combined sources | 7 | |
Beta strandi | 570 – 575 | Combined sources | 6 | |
Beta strandi | 588 – 596 | Combined sources | 9 | |
Beta strandi | 609 – 618 | Combined sources | 10 | |
Helixi | 620 – 635 | Combined sources | 16 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4YNZ | X-ray | 2.00 | A/B | 15-342 | [»] | |
4YOM | X-ray | 2.49 | A | 519-662 | [»] | |
B | 1-342 | [»] | ||||
ProteinModelPortali | Q69Z98. | |||||
SMRi | Q69Z98. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 20 – 271 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 | |
Domaini | 298 – 340 | UBAAdd BLAST | 43 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 604 – 606 | KEN boxBy similarity | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 425 – 469 | Pro-richAdd BLAST | 45 |
Domaini
The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0588. Eukaryota. ENOG410XNQ0. LUCA. |
GeneTreei | ENSGT00900000140977. |
HOGENOMi | HOG000246447. |
HOVERGENi | HBG007240. |
InParanoidi | Q69Z98. |
KOi | K08796. |
OMAi | HRRKMSN. |
OrthoDBi | EOG091G02CG. |
PhylomeDBi | Q69Z98. |
TreeFami | TF313967. |
Family and domain databases
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. |
Pfami | View protein in Pfam PF00069. Pkinase. 1 hit. |
SMARTi | View protein in SMART SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF56112. SSF56112. 2 hits. |
PROSITEi | View protein in PROSITE PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q69Z98-1) [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.
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 PESSPELAKK SWFGNFINLE KEEQIFVVIK DKPLSSIKAD
560 570 580 590 600
IVHAFLSIPS LSHSVISQTS FRAEYKATGG PAVFQKPVKF QVDITYTEGG
610 620 630 640 650
EAQKENGIYS VTFTLLSGPS RRFKRVVETI QAQLLSTHDQ PSAQHLSDTT
660 670 680 690 700
NCMEVMTGRL SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG
710 720 730
PLGDSAAAGP GGDTEYPMGK DMAKMGPPAA RREQP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 31 – 43 | TGLVK…HCVTC → VDGDLLASDTVDS in BAD32546 (PubMed:15368895).CuratedAdd BLAST | 13 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_022605 | 648 – 735 | DTTNC…RREQP → EPPPPAPGLSWGAGLKGQKV ATSYESSL in isoform 2. 1 PublicationAdd BLAST | 88 | |
Alternative sequenceiVSP_022607 | 648 – 653 | DTTNCM → GIIPKS in isoform 4. 3 Publications | 6 | |
Alternative sequenceiVSP_022608 | 654 – 735 | Missing in isoform 4. 3 PublicationsAdd BLAST | 82 | |
Alternative sequenceiVSP_022606 | 664 – 679 | Missing in isoform 3. 1 PublicationAdd BLAST | 16 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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. |
CCDSi | CCDS22021.1. [Q69Z98-4] CCDS22022.1. [Q69Z98-3] CCDS22023.1. [Q69Z98-2] |
RefSeqi | NP_001009929.1. NM_001009929.3. [Q69Z98-2] NP_001009930.1. NM_001009930.3. [Q69Z98-3] NP_083702.1. NM_029426.2. [Q69Z98-4] |
UniGenei | Mm.274868. Mm.482784. |
Genome annotation databases
Ensembli | ENSMUST00000018971; ENSMUSP00000018971; ENSMUSG00000053046. [Q69Z98-4] ENSMUST00000075528; ENSMUSP00000074969; ENSMUSG00000053046. [Q69Z98-3] ENSMUST00000078200; ENSMUSP00000077330; ENSMUSG00000053046. [Q69Z98-2] ENSMUST00000105989; ENSMUSP00000101610; ENSMUSG00000053046. [Q69Z98-2] ENSMUST00000174499; ENSMUSP00000134201; ENSMUSG00000053046. [Q69Z98-1] |
GeneIDi | 75770. |
KEGGi | mmu:75770. |
UCSCi | uc009kme.2. mouse. [Q69Z98-2] uc009kmf.2. mouse. [Q69Z98-3] uc009kmg.1. mouse. [Q69Z98-4] uc009kmi.1. mouse. [Q69Z98-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | BRSK2_MOUSE | |
Accessioni | Q69Z98Primary (citable) accession number: Q69Z98 Secondary accession number(s): Q699J3 Q6PHM0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 23, 2007 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 28, 2018 | |
This is version 124 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |