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Protein

Serine/threonine-protein kinase BRSK2

Gene

Brsk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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-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 endoplasmatic 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1
Active sitei142Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATPase binding Source: MGI
  • ATP binding Source: MGI
  • magnesium ion binding Source: UniProtKB
  • 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
  • mitotic nuclear division Source: UniProtKB-KW
  • 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
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:Kiaa4256, Sada
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1923020. Brsk2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endoplasmic reticulum

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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi175T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002740361 – 735Serine/threonine-protein kinase BRSK2Add BLAST735

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei175Phosphothreonine; by LKB11 Publication1
Modified residuei261Phosphothreonine; by PKABy similarity1
Modified residuei295PhosphoserineBy similarity1
Modified residuei368PhosphoserineBy similarity1
Modified residuei383PhosphoserineCombined sources1
Modified residuei394PhosphoserineCombined sources1
Modified residuei413PhosphoserineCombined sources1
Modified residuei423PhosphothreonineBy similarity1
Modified residuei424PhosphoserineCombined sources1
Modified residuei428PhosphoserineCombined sources1
Modified residuei456PhosphoserineCombined sources1
Modified residuei460PhosphothreonineCombined sources1
Modified residuei464PhosphothreonineCombined sources1
Modified residuei510PhosphothreonineCombined sources1
Modified residuei513PhosphoserineCombined sources1
Modified residuei514PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1

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 conjugation

Proteomic databases

PaxDbiQ69Z98.
PeptideAtlasiQ69Z98.
PRIDEiQ69Z98.

PTM databases

iPTMnetiQ69Z98.
PhosphoSitePlusiQ69Z98.

Expressioni

Tissue specificityi

Detected in pancreas islets and in brain (at protein level). Detected in brain and pancreas.1 Publication

Gene expression databases

BgeeiENSMUSG00000053046.
CleanExiMM_BRSK2.
ExpressionAtlasiQ69Z98. baseline and differential.
GenevisibleiQ69Z98. 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

BioGridi217728. 1 interactor.
STRINGi10090.ENSMUSP00000074969.

Structurei

Secondary structure

1735
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi15 – 17Combined sources3
Beta strandi20 – 29Combined sources10
Beta strandi32 – 39Combined sources8
Turni40 – 42Combined sources3
Beta strandi45 – 53Combined sources9
Helixi58 – 71Combined sources14
Beta strandi82 – 87Combined sources6
Beta strandi89 – 96Combined sources8
Helixi104 – 111Combined sources8
Helixi116 – 135Combined sources20
Helixi145 – 147Combined sources3
Beta strandi148 – 150Combined sources3
Beta strandi156 – 158Combined sources3
Helixi164 – 166Combined sources3
Beta strandi172 – 174Combined sources3
Helixi180 – 182Combined sources3
Helixi185 – 188Combined sources4
Helixi195 – 212Combined sources18
Helixi222 – 231Combined sources10
Helixi242 – 251Combined sources10
Turni256 – 258Combined sources3
Helixi262 – 266Combined sources5
Helixi269 – 272Combined sources4
Turni274 – 276Combined sources3
Helixi296 – 298Combined sources3
Helixi301 – 308Combined sources8
Helixi311 – 313Combined sources3
Helixi316 – 324Combined sources9
Beta strandi325 – 327Combined sources3
Helixi330 – 342Combined sources13
Beta strandi520 – 523Combined sources4
Turni524 – 526Combined sources3
Beta strandi530 – 532Combined sources3
Beta strandi534 – 539Combined sources6
Helixi544 – 556Combined sources13
Beta strandi561 – 567Combined sources7
Beta strandi570 – 575Combined sources6
Beta strandi588 – 596Combined sources9
Beta strandi609 – 618Combined sources10
Helixi620 – 635Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YNZX-ray2.00A/B15-342[»]
4YOMX-ray2.49A519-662[»]
B1-342[»]
ProteinModelPortaliQ69Z98.
SMRiQ69Z98.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 271Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini298 – 340UBAAdd BLAST43

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi604 – 606KEN boxBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi425 – 469Pro-richAdd BLAST45

Domaini

The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.Curated

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOGENOMiHOG000246447.
HOVERGENiHBG007240.
InParanoidiQ69Z98.
KOiK08796.
OMAiNCMELMT.
OrthoDBiEOG091G02CG.
PhylomeDBiQ69Z98.
TreeFamiTF313967.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative 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.

« 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 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
Length:735
Mass (Da):81,733
Last modified:January 23, 2007 - v2
Checksum:iA37FCC6CC7253F11
GO
Isoform 2 (identifier: Q69Z98-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:675
Mass (Da):75,361
Checksum:iB01D8D8F9C24C71F
GO
Isoform 3 (identifier: Q69Z98-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:719
Mass (Da):79,938
Checksum:i4C2ABA57205974AB
GO
Isoform 4 (identifier: Q69Z98-4) [UniParc]FASTAAdd to basket
Also known as: SADA-alpha

The sequence of this isoform differs from the canonical sequence as follows:
     648-653: DTTNCM → GIIPKS
     654-735: Missing.

Show »
Length:653
Mass (Da):73,150
Checksum:i8A23B94D71850E9A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31 – 43TGLVK…HCVTC → VDGDLLASDTVDS in BAD32546 (PubMed:15368895).CuratedAdd BLAST13

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022605648 – 735DTTNC…RREQP → EPPPPAPGLSWGAGLKGQKV ATSYESSL in isoform 2. 1 PublicationAdd BLAST88
Alternative sequenceiVSP_022607648 – 653DTTNCM → GIIPKS in isoform 4. 3 Publications6
Alternative sequenceiVSP_022608654 – 735Missing in isoform 4. 3 PublicationsAdd BLAST82
Alternative sequenceiVSP_022606664 – 679Missing in isoform 3. 1 PublicationAdd BLAST16

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.
CCDSiCCDS22021.1. [Q69Z98-4]
CCDS22022.1. [Q69Z98-3]
CCDS22023.1. [Q69Z98-2]
RefSeqiNP_001009929.1. NM_001009929.3. [Q69Z98-2]
NP_001009930.1. NM_001009930.3. [Q69Z98-3]
NP_083702.1. NM_029426.2. [Q69Z98-4]
UniGeneiMm.274868.
Mm.482784.

Genome annotation databases

EnsembliENSMUST00000018971; ENSMUSP00000018971; ENSMUSG00000053046. [Q69Z98-4]
ENSMUST00000075528; ENSMUSP00000074969; ENSMUSG00000053046. [Q69Z98-3]
ENSMUST00000078200; ENSMUSP00000077330; ENSMUSG00000053046. [Q69Z98-2]
ENSMUST00000105989; ENSMUSP00000101610; ENSMUSG00000053046. [Q69Z98-2]
ENSMUST00000174499; ENSMUSP00000134201; ENSMUSG00000053046. [Q69Z98-1]
GeneIDi75770.
KEGGimmu:75770.
UCSCiuc009kme.2. mouse. [Q69Z98-2]
uc009kmf.2. mouse. [Q69Z98-3]
uc009kmg.1. mouse. [Q69Z98-4]
uc009kmi.1. mouse. [Q69Z98-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS22021.1. [Q69Z98-4]
CCDS22022.1. [Q69Z98-3]
CCDS22023.1. [Q69Z98-2]
RefSeqiNP_001009929.1. NM_001009929.3. [Q69Z98-2]
NP_001009930.1. NM_001009930.3. [Q69Z98-3]
NP_083702.1. NM_029426.2. [Q69Z98-4]
UniGeneiMm.274868.
Mm.482784.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YNZX-ray2.00A/B15-342[»]
4YOMX-ray2.49A519-662[»]
B1-342[»]
ProteinModelPortaliQ69Z98.
SMRiQ69Z98.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi217728. 1 interactor.
STRINGi10090.ENSMUSP00000074969.

PTM databases

iPTMnetiQ69Z98.
PhosphoSitePlusiQ69Z98.

Proteomic databases

PaxDbiQ69Z98.
PeptideAtlasiQ69Z98.
PRIDEiQ69Z98.

Protocols and materials databases

DNASUi75770.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000018971; ENSMUSP00000018971; ENSMUSG00000053046. [Q69Z98-4]
ENSMUST00000075528; ENSMUSP00000074969; ENSMUSG00000053046. [Q69Z98-3]
ENSMUST00000078200; ENSMUSP00000077330; ENSMUSG00000053046. [Q69Z98-2]
ENSMUST00000105989; ENSMUSP00000101610; ENSMUSG00000053046. [Q69Z98-2]
ENSMUST00000174499; ENSMUSP00000134201; ENSMUSG00000053046. [Q69Z98-1]
GeneIDi75770.
KEGGimmu:75770.
UCSCiuc009kme.2. mouse. [Q69Z98-2]
uc009kmf.2. mouse. [Q69Z98-3]
uc009kmg.1. mouse. [Q69Z98-4]
uc009kmi.1. mouse. [Q69Z98-1]

Organism-specific databases

CTDi9024.
MGIiMGI:1923020. Brsk2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOGENOMiHOG000246447.
HOVERGENiHBG007240.
InParanoidiQ69Z98.
KOiK08796.
OMAiNCMELMT.
OrthoDBiEOG091G02CG.
PhylomeDBiQ69Z98.
TreeFamiTF313967.

Miscellaneous databases

PROiQ69Z98.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000053046.
CleanExiMM_BRSK2.
ExpressionAtlasiQ69Z98. baseline and differential.
GenevisibleiQ69Z98. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBRSK2_MOUSE
AccessioniPrimary (citable) accession number: Q69Z98
Secondary accession number(s): Q699J3
, Q699J4, Q6DMN7, Q6PHM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.