UniProtKB - Q69Z98 (BRSK2_MOUSE)
Serine/threonine-protein kinase BRSK2
Brsk2
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 PublicationsCatalytic activityi
- EC:2.7.11.11 Publication
- EC:2.7.11.11 Publication
- EC:2.7.11.261 Publication
- EC:2.7.11.261 Publication
Cofactori
Activity regulationi
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/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- tau-protein kinase activity Source: UniProtKB
GO - Biological processi
- actin cytoskeleton reorganization Source: MGI
- axonogenesis Source: UniProtKB
- cell division Source: UniProtKB-KW
- cellular response to glucose starvation Source: GO_Central
- 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
- microtubule cytoskeleton organization involved in establishment of planar polarity Source: ARUK-UCL
- neuron differentiation Source: UniProtKB
- neuron projection morphogenesis Source: MGI
- peptidyl-serine phosphorylation Source: MGI
- protein phosphorylation Source: UniProtKB
- regulation of axonogenesis Source: ARUK-UCL
- regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
- regulation of neuron projection development Source: ARUK-UCL
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 |
VEuPathDBi | HostDB:ENSMUSG00000053046 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Cytoskeleton
- centrosome By similarity
Other locations
- perinuclear region By similarity
Note: Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin (By similarity).By similarity
Cytoskeleton
- centrosome Source: MGI
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
Other locations
- cytoplasm Source: MGI
- distal axon Source: MGI
- perinuclear region of cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Endoplasmic reticulumPathology & Biotechi
Disruption phenotypei
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
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | Q69Z98 |
PaxDbi | Q69Z98 |
PeptideAtlasi | Q69Z98 |
PRIDEi | Q69Z98 |
ProteomicsDBi | 273769 [Q69Z98-1] 273770 [Q69Z98-2] 273771 [Q69Z98-3] 273772 [Q69Z98-4] |
PTM databases
iPTMneti | Q69Z98 |
PhosphoSitePlusi | Q69Z98 |
SwissPalmi | Q69Z98 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000053046, Expressed in visual cortex and 170 other tissues |
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 similarityGO - Molecular functioni
- ATPase binding Source: MGI
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 217728, 8 interactors |
STRINGi | 10090.ENSMUSP00000134201 |
Miscellaneous databases
RNActi | Q69Z98, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q69Z98 |
ModBasei | Search... |
PDBe-KBi | 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 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 346 – 476 | DisorderedSequence analysisAdd BLAST | 131 | |
Regioni | 492 – 516 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 682 – 735 | DisorderedSequence analysisAdd BLAST | 54 |
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 | 346 – 385 | Basic and acidic residuesSequence analysisAdd BLAST | 40 | |
Compositional biasi | 408 – 429 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 430 – 470 | Pro residuesSequence analysisAdd BLAST | 41 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0588, Eukaryota |
GeneTreei | ENSGT00940000157462 |
HOGENOMi | CLU_000288_156_2_1 |
InParanoidi | Q69Z98 |
OMAi | VMAENCQ |
OrthoDBi | 1127668at2759 |
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, 1 hit |
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 basketThis entry has 4 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3UZ19 | G3UZ19_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 486 | Annotation score: | ||
G3UWV4 | G3UWV4_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 697 | Annotation score: | ||
G3UXM5 | G3UXM5_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 614 | Annotation score: | ||
G3UYP7 | G3UYP7_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 113 | Annotation score: | ||
G3UYN4 | G3UYN4_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 504 | Annotation score: | ||
G3UZ00 | G3UZ00_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 92 | Annotation score: | ||
G3UZN4 | G3UZN4_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 232 | Annotation score: | ||
G3UXY1 | G3UXY1_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 200 | Annotation score: | ||
G5E921 | G5E921_MOUSE | Serine/threonine-protein kinase BRS... | Brsk2 | 47 | Annotation score: |
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] |
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
Cross-referencesi
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] |
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 | [»] | ||||
SMRi | Q69Z98 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 217728, 8 interactors |
STRINGi | 10090.ENSMUSP00000134201 |
PTM databases
iPTMneti | Q69Z98 |
PhosphoSitePlusi | Q69Z98 |
SwissPalmi | Q69Z98 |
Proteomic databases
MaxQBi | Q69Z98 |
PaxDbi | Q69Z98 |
PeptideAtlasi | Q69Z98 |
PRIDEi | Q69Z98 |
ProteomicsDBi | 273769 [Q69Z98-1] 273770 [Q69Z98-2] 273771 [Q69Z98-3] 273772 [Q69Z98-4] |
Protocols and materials databases
Antibodypediai | 22872, 226 antibodies from 34 providers |
DNASUi | 75770 |
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] |
Organism-specific databases
CTDi | 9024 |
MGIi | MGI:1923020, Brsk2 |
VEuPathDBi | HostDB:ENSMUSG00000053046 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG0588, Eukaryota |
GeneTreei | ENSGT00940000157462 |
HOGENOMi | CLU_000288_156_2_1 |
InParanoidi | Q69Z98 |
OMAi | VMAENCQ |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q69Z98 |
TreeFami | TF313967 |
Miscellaneous databases
BioGRID-ORCSi | 75770, 1 hit in 66 CRISPR screens |
PROi | PR:Q69Z98 |
RNActi | Q69Z98, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000053046, Expressed in visual cortex and 170 other tissues |
Genevisiblei | Q69Z98, MM |
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, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
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 23, 2022 | |
This is version 146 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families