B2DD29 (BRSK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase BRSK1
EC=2.7.11.1
EC=2.7.11.26

Alternative name(s):
Brain-specific serine/threonine-protein kinase 1
Short name=BR serine/threonine-protein kinase 1
Serine/threonine-protein kinase SAD-B

Gene names

Name:	Brsk1
Synonyms:	Sadb

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	778 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 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-523' and 'Ser-573'. 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. 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 By similarity. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + [tau protein] = ADP + [tau protein] phosphate.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphorylation on Thr-189 by STK11/LKB1.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Cell junction › synapse. Note: Nuclear in the absence of DNA damage. Translocated to the nucleus in response to UV- or MMS-induced DNA damage By similarity. Localizes to synaptic vesicles in neurons. Ref.3
Tissue specificity	Mainly present in brain. Present in presynaptic nerve terminals (at protein level). Ref.3
Post-translational modification	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. May be autophosphorylated. Ref.1 Ref.3
Miscellaneous	Protein synthesis is inhibited by the TSC1-TSC2 complex acting through TORC1 in neurons, leading to regulate neuron polarization (Ref.4).
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

Keywords
Biological process	Cell cycle DNA damage Neurogenesis
Cellular component	Cell junction Cytoplasm Cytoskeleton Nucleus Synapse
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2 DNA damage checkpoint Inferred from electronic annotation. Source: Compara axonogenesis Inferred from sequence or structural similarity. Source: UniProtKB centrosome duplication Inferred from sequence or structural similarity. Source: UniProtKB establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB neurotransmitter secretion Inferred from mutant phenotype Ref.3. Source: UniProtKB protein autophosphorylation Traceable author statement Ref.3. Source: UniProtKB response to UV Inferred from electronic annotation. Source: Compara
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW centrosome Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from direct assay Ref.3. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW gamma-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Inferred from direct assay Ref.3. Source: UniProtKB tau-protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 778	778	Serine/threonine-protein kinase BRSK1		PRO_0000412649
Regions
	Domain	34 – 285	252	Protein kinase
	Domain	314 – 356	43	UBA
	Nucleotide binding	40 – 48	9	ATP By similarity
	Compositional bias	492 – 540	49	Pro-rich
Sites
	Active site	156	1	Proton acceptor By similarity
	Binding site	63	1	ATP By similarity
Amino acid modifications
	Modified residue	189	1	Phosphothreonine; by LKB1 Ref.1
	Modified residue	193	1	Phosphoserine Probable
	Modified residue	447	1	Phosphoserine By similarity
	Modified residue	508	1	Phosphoserine By similarity
	Modified residue	563	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	63	1	K → R: Abolishes kinase activity. Ref.3
	Mutagenesis	189	1	T → A: Decreased autophosphorylation; when associated with A-193. Ref.3
	Mutagenesis	193	1	S → A: Decreased autophosphorylation; when associated with A-189. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	B2DD29 [UniParc]. Last modified June 10, 2008. Version 1. Checksum: A4F1E7E107359BDD	FASTA	778	85,183
	10 20 30 40 50 60 MSSGSKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL GVHCITGQKV 70 80 90 100 110 120 AVKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY ENKKYLYLVL EHVSGGELFD 130 140 150 160 170 180 YLVKKGRLTP KEARKFFRQI VSALDFCHSY SICHRDLKPE NLLLDEKNNI RIADFGMASL 190 200 210 220 230 240 QVGDSLLETS CGSPHYACPE VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL 250 260 270 280 290 300 EKVKRGVFHM PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP 310 320 330 340 350 360 GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI YYLLLDRKER 370 380 390 400 410 420 YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM EVLSITDAGS GGSPVPTRRA 430 440 450 460 470 480 LEMAQHSQRS RSVSGASTGL SSSPLSSPRS PVFSFSPEPG VGDEARGGGS PTSKTQTLPS 490 500 510 520 530 540 RGPRGGGAGE QPPPPSARST PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP 550 560 570 580 590 600 GGGVGGAAWR SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI 610 620 630 640 650 660 SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA SGGPSVFQKP 670 680 690 700 710 720 VRFQVDISSS EGPEPSPRRD GSSGGGIYSV TFTLISGPSR RFKRVVETIQ AQLLSTHDQP 730 740 750 760 770 SVQALADEKN GAQTRPAGTP PRSLQPPPGR PDPDLSSSPR RGPSKDKKLL ATNGTPLP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of SAD kinase by Ca2+/calmodulin-dependent protein kinase kinase." Fujimoto T., Yurimoto S., Hatano N., Nozaki N., Sueyoshi N., Kameshita I., Mizutani A., Mikoshiba K., Kobayashi R., Tokumitsu H. Biochemistry 47:4151-4159(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-189. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[3]	"SAD: a presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release." Inoue E., Mochida S., Takagi H., Higa S., Deguchi-Tawarada M., Takao-Rikitsu E., Inoue M., Yao I., Takeuchi K., Kitajima I., Setou M., Ohtsuka T., Takai Y. Neuron 50:261-275(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTPHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-63; THR-189 AND SER-193.
[4]	"Tuberous sclerosis complex proteins control axon formation." Choi Y.J., Di Nardo A., Kramvis I., Meikle L., Kwiatkowski D.J., Sahin M., He X. Genes Dev. 22:2485-2495(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REGULATION OF TRANSLATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB365521 mRNA. Translation: BAG28183.1.
IPI	IPI00896186.
RefSeq	NP_001120809.1. NM_001127337.1.
UniGene	Rn.112844.
3D structure databases
ProteinModelPortal	B2DD29.
ModBase	Search...
Proteomic databases
PaxDb	B2DD29.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000031172; ENSRNOP00000033679; ENSRNOG00000017673.
GeneID	499073.
KEGG	rno:499073.
UCSC	RGD:1563268. rat.
Organism-specific databases
CTD	84446.
RGD	1563268. Brsk1.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000246447.
HOVERGEN	HBG007240.
KO	K08796.
OrthoDB	EOG479F6K.
Gene expression databases
Genevestigator	B2DD29.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	701750.

Entry information

Entry name

BRSK1_RAT

Accession

Primary (citable) accession number: B2DD29
Secondary accession number(s): F1M6Y8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 21, 2011
Last sequence update:	June 10, 2008
Last modified:	May 1, 2013
This is version 38 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program