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Protein

Serine/threonine-protein kinase BRSK1

Gene

BRSK1

Organism
Homo sapiens (Human)
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 centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 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-529' and 'Ser-579'. 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. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.4 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-189 by STK11/LKB1.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei63ATPPROSITE-ProRule annotation1
Active sitei156Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 48ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • gamma-tubulin binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  • axonogenesis Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • centrosome duplication Source: UniProtKB
  • establishment of cell polarity Source: UniProtKB
  • G2 DNA damage checkpoint Source: UniProtKB
  • intracellular signal transduction Source: GO_Central
  • neuron differentiation Source: UniProtKB
  • neurotransmitter secretion Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • response to UV Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, DNA damage, Neurogenesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS08504-MONOMER.
SignaLinkiQ8TDC3.
SIGNORiQ8TDC3.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase BRSK1 (EC:2.7.11.1)
Alternative name(s):
Brain-selective kinase 1 (EC:2.7.11.26)
Brain-specific serine/threonine-protein kinase 1
Short name:
BR serine/threonine-protein kinase 1
Serine/threonine-protein kinase SAD-B
Synapses of Amphids Defective homolog 1
Short name:
SAD1 homolog
Short name:
hSAD1
Gene namesi
Name:BRSK1
Synonyms:KIAA1811, SAD1, SADB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:18994. BRSK1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
  • Cell junctionsynapse By similarity

  • Note: Localizes to synaptic vesicles in neurons (By similarity). Nuclear in the absence of DNA damage. Translocated to the nucleus in response to UV- or MMS-induced DNA damage.By similarity

GO - Cellular componenti

  • cell junction Source: HPA
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • synaptic vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoskeleton, Nucleus, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi59K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi189T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication1
Mutagenesisi327G → A: Abolishes activation of kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi84446.
OpenTargetsiENSG00000160469.
PharmGKBiPA134888976.

Chemistry databases

ChEMBLiCHEMBL5650.
GuidetoPHARMACOLOGYi1946.

Polymorphism and mutation databases

BioMutaiBRSK1.
DMDMi347595639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856691 – 778Serine/threonine-protein kinase BRSK1Add BLAST778

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei189Phosphothreonine; by LKB12 Publications1
Modified residuei399PhosphoserineBy similarity1
Modified residuei443PhosphoserineBy similarity1
Modified residuei447Phosphoserine1 Publication1
Modified residuei450PhosphoserineBy similarity1
Modified residuei466Omega-N-methylarginineBy similarity1
Modified residuei481Omega-N-methylarginineBy similarity1
Modified residuei484Omega-N-methylarginineBy similarity1
Modified residuei498Omega-N-methylarginineBy similarity1
Modified residuei508PhosphoserineCombined sources1
Modified residuei525Omega-N-methylarginineBy similarity1
Modified residuei529PhosphothreonineBy similarity1
Modified residuei535PhosphothreonineBy similarity1
Modified residuei550Omega-N-methylarginineBy similarity1
Modified residuei563Phosphoserine1 Publication1
Modified residuei583PhosphothreonineBy similarity1
Modified residuei586PhosphoserineBy similarity1
Modified residuei587PhosphoserineBy similarity1
Modified residuei601PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-189 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-189 by PP2C.3 Publications

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ8TDC3.
PeptideAtlasiQ8TDC3.
PRIDEiQ8TDC3.

PTM databases

iPTMnetiQ8TDC3.
PhosphoSitePlusiQ8TDC3.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in brain and testis. Protein levels remain constant throughout the cell cycle.1 Publication

Gene expression databases

BgeeiENSG00000160469.
CleanExiHS_BRSK1.
ExpressionAtlasiQ8TDC3. baseline and differential.
GenevisibleiQ8TDC3. HS.

Organism-specific databases

HPAiHPA021212.
HPA061719.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124084. 4 interactors.
IntActiQ8TDC3. 3 interactors.
MINTiMINT-1651556.
STRINGi9606.ENSP00000310649.

Chemistry databases

BindingDBiQ8TDC3.

Structurei

3D structure databases

ProteinModelPortaliQ8TDC3.
SMRiQ8TDC3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 285Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini314 – 356UBAPROSITE-ProRule annotationAdd BLAST43

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi492 – 540Pro-richAdd BLAST49

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOVERGENiHBG007240.
InParanoidiQ8TDC3.
KOiK08796.
OMAiGRHAQYV.
OrthoDBiEOG091G02CG.
PhylomeDBiQ8TDC3.
TreeFamiTF313967.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[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.
PS50030. UBA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TDC3-1) [UniParc]FASTAAdd to basket
Also known as: SADB-Long, L

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
MSSGAKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL
60 70 80 90 100
GVHCITGQKV AIKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY
110 120 130 140 150
ENKKYLYLVL EHVSGGELFD YLVKKGRLTP KEARKFFRQI VSALDFCHSY
160 170 180 190 200
SICHRDLKPE NLLLDEKNNI RIADFGMASL QVGDSLLETS CGSPHYACPE
210 220 230 240 250
VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL EKVKRGVFHM
260 270 280 290 300
PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP
310 320 330 340 350
GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI
360 370 380 390 400
YYLLLDRKER YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM
410 420 430 440 450
EVLSITDAGG GGSPVPTRRA LEMAQHSQRS RSVSGASTGL SSSPLSSPRS
460 470 480 490 500
PVFSFSPEPG AGDEARGGGS PTSKTQTLPS RGPRGGGAGE QPPPPSARST
510 520 530 540 550
PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP GGGVGGAAWR
560 570 580 590 600
SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI
610 620 630 640 650
SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA
660 670 680 690 700
SGGPSVFQKP VRFQVDISSS EGPEPSPRRD GSGGGGIYSV TFTLISGPSR
710 720 730 740 750
RFKRVVETIQ AQLLSTHDQP SVQALADEKN GAQTRPAGAP PRSLQPPPGR
760 770
PDPELSSSPR RGPPKDKKLL ATNGTPLP
Length:778
Mass (Da):85,087
Last modified:September 21, 2011 - v2
Checksum:i8D1818D4E54398BB
GO
Isoform 2 (identifier: Q8TDC3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MSSGAKEGGGGSPAYHLPHPHPHPPQ → MVAGLTLGKGPESPDGDVSVPERKDEVAGGGGEEEEAEERGR

Show »
Length:794
Mass (Da):86,753
Checksum:i5DD395B0E61AEF77
GO
Isoform 3 (identifier: Q8TDC3-3) [UniParc]FASTAAdd to basket
Also known as: SADB-short, S

The sequence of this isoform differs from the canonical sequence as follows:
     344-778: Missing.

Show »
Length:343
Mass (Da):38,782
Checksum:i225C16D92E18BD8C
GO

Sequence cautioni

The sequence AAH16681 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti762G → A in AAH16681 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040394303R → W in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs144130246dbSNPEnsembl.1
Natural variantiVAR_040395319V → I in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040396391G → E in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040397531T → N.1 PublicationCorresponds to variant rs55892637dbSNPEnsembl.1
Natural variantiVAR_040398749G → S.1 PublicationCorresponds to variant rs12978445dbSNPEnsembl.1
Natural variantiVAR_040399764P → A.1 PublicationCorresponds to variant rs55796422dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0081581 – 26MSSGA…PHPPQ → MVAGLTLGKGPESPDGDVSV PERKDEVAGGGGEEEEAEER GR in isoform 2. 2 PublicationsAdd BLAST26
Alternative sequenceiVSP_041742344 – 778Missing in isoform 3. 1 PublicationAdd BLAST435

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY458602 mRNA. Translation: AAS10354.1.
AY505124 mRNA. Translation: AAS86442.1.
HQ830199 mRNA. Translation: ADX95745.1.
AF479826 mRNA. Translation: AAL87697.1.
AF479827 mRNA. Translation: AAL87698.1.
AC008974 Genomic DNA. No translation available.
AC020922 Genomic DNA. No translation available.
AL831945 mRNA. Translation: CAD38595.1.
AL834275 mRNA. Translation: CAD38950.2.
AB058714 mRNA. Translation: BAB47440.1.
BC016681 mRNA. Translation: AAH16681.1. Different initiation.
CCDSiCCDS12921.1. [Q8TDC3-1]
RefSeqiNP_115806.1. NM_032430.1. [Q8TDC3-1]
UniGeneiHs.182081.

Genome annotation databases

EnsembliENST00000309383; ENSP00000310649; ENSG00000160469. [Q8TDC3-1]
ENST00000585418; ENSP00000467357; ENSG00000160469. [Q8TDC3-3]
ENST00000590333; ENSP00000468190; ENSG00000160469. [Q8TDC3-2]
GeneIDi84446.
KEGGihsa:84446.
UCSCiuc002qkf.4. human. [Q8TDC3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY458602 mRNA. Translation: AAS10354.1.
AY505124 mRNA. Translation: AAS86442.1.
HQ830199 mRNA. Translation: ADX95745.1.
AF479826 mRNA. Translation: AAL87697.1.
AF479827 mRNA. Translation: AAL87698.1.
AC008974 Genomic DNA. No translation available.
AC020922 Genomic DNA. No translation available.
AL831945 mRNA. Translation: CAD38595.1.
AL834275 mRNA. Translation: CAD38950.2.
AB058714 mRNA. Translation: BAB47440.1.
BC016681 mRNA. Translation: AAH16681.1. Different initiation.
CCDSiCCDS12921.1. [Q8TDC3-1]
RefSeqiNP_115806.1. NM_032430.1. [Q8TDC3-1]
UniGeneiHs.182081.

3D structure databases

ProteinModelPortaliQ8TDC3.
SMRiQ8TDC3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124084. 4 interactors.
IntActiQ8TDC3. 3 interactors.
MINTiMINT-1651556.
STRINGi9606.ENSP00000310649.

Chemistry databases

BindingDBiQ8TDC3.
ChEMBLiCHEMBL5650.
GuidetoPHARMACOLOGYi1946.

PTM databases

iPTMnetiQ8TDC3.
PhosphoSitePlusiQ8TDC3.

Polymorphism and mutation databases

BioMutaiBRSK1.
DMDMi347595639.

Proteomic databases

PaxDbiQ8TDC3.
PeptideAtlasiQ8TDC3.
PRIDEiQ8TDC3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309383; ENSP00000310649; ENSG00000160469. [Q8TDC3-1]
ENST00000585418; ENSP00000467357; ENSG00000160469. [Q8TDC3-3]
ENST00000590333; ENSP00000468190; ENSG00000160469. [Q8TDC3-2]
GeneIDi84446.
KEGGihsa:84446.
UCSCiuc002qkf.4. human. [Q8TDC3-1]

Organism-specific databases

CTDi84446.
DisGeNETi84446.
GeneCardsiBRSK1.
H-InvDBHIX0015461.
HGNCiHGNC:18994. BRSK1.
HPAiHPA021212.
HPA061719.
MIMi609235. gene.
neXtProtiNX_Q8TDC3.
OpenTargetsiENSG00000160469.
PharmGKBiPA134888976.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0588. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00860000133738.
HOVERGENiHBG007240.
InParanoidiQ8TDC3.
KOiK08796.
OMAiGRHAQYV.
OrthoDBiEOG091G02CG.
PhylomeDBiQ8TDC3.
TreeFamiTF313967.

Enzyme and pathway databases

BioCyciZFISH:HS08504-MONOMER.
SignaLinkiQ8TDC3.
SIGNORiQ8TDC3.

Miscellaneous databases

ChiTaRSiBRSK1. human.
GeneWikiiBRSK1.
GenomeRNAii84446.
PROiQ8TDC3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160469.
CleanExiHS_BRSK1.
ExpressionAtlasiQ8TDC3. baseline and differential.
GenevisibleiQ8TDC3. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[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.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBRSK1_HUMAN
AccessioniPrimary (citable) accession number: Q8TDC3
Secondary accession number(s): F1DG44
, Q5J5B5, Q8NDD0, Q8NDR4, Q8TDC2, Q96AV4, Q96JL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: September 21, 2011
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.