Q8IWQ3 (BRSK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase BRSK2
EC=2.7.11.1

Alternative name(s):
Brain-selective kinase 2
EC=2.7.11.26
Brain-specific serine/threonine-protein kinase 2
Short name=BR serine/threonine-protein kinase 2
Serine/threonine-protein kinase 29
Serine/threonine-protein kinase SAD-A

Gene names

Name:	BRSK2
Synonyms:	C11orf7, PEN11B, SADA, STK29
ORF Names:	HUSSY-12

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	736 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 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-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. 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-174 can inhibit insulin secretion (Ref.18), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (Ref.17). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmatic reticulum (ER) stress. Ref.8 Ref.14 Ref.17 Ref.18 Ref.19 Ref.20
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.18 Ref.19 ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.18 Ref.19
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphorylation on Thr-174 by STK11/LKB1. Ref.8
Subunit structure	Interacts with FZR1, a regulatory subunit of the APC ubiquitin ligase complex. Interacts with COPS5. Interacts with PAK1. Ref.15 Ref.17 Ref.20
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Cytoplasm › perinuclear region. Endoplasmic reticulum. Note: Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin. Ref.15 Ref.16 Ref.20
Tissue specificity	Detected in pancreas islets (at protein level). Ref.18
Domain	The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.
Post-translational modification	Phosphorylated at Thr-174 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-174 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-174 by PP2C. Phosphorylated at Thr-260 by PKA. Phosphorylation at Thr-260 by PKA was not observed in another study (Ref.10), but this may reflect differences in the experimental approach. Phosphorylation at Thr-260 seems to play a role in the regulation of insulin secretion (Ref.17). Ref.8 Ref.9 Ref.10 Ref.13 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.
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.
Sequence caution	The sequence AAD09654.1 differs from that shown. Reason: Erroneous termination at position 663. Translated as Gly. The sequence AAD09654.1 differs from that shown. Reason: Frameshift at position 640. The sequence AAH24291.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Exocytosis Mitosis Neurogenesis
Cellular component	Cytoplasm Cytoskeleton Endoplasmic reticulum
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2/M transition of mitotic cell cycle Inferred from mutant phenotype Ref.20. Source: UniProtKB actin cytoskeleton reorganization Inferred from mutant phenotype Ref.17. Source: UniProtKB axonogenesis Inferred from sequence or structural similarity. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB exocytosis Inferred from electronic annotation. Source: UniProtKB-KW intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from mutant phenotype Ref.16. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from mutant phenotype Ref.17. Source: UniProtKB
Cellular_component	centrosome Inferred from direct assay Ref.20. Source: UniProtKB cytoplasm Inferred from direct assay Ref.16. Source: UniProtKB endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay Ref.8. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.8. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.8. Source: UniProtKB tau-protein kinase activity Inferred from direct assay Ref.19. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IWQ3-1)

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.

Isoform 2 (identifier: Q8IWQ3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     647-674: DTTNCMEMMTGRLSKCGSPLSNFFDVIK → EPPPPAPGLSWGAGLKGQKVATSYESSL
     675-736: Missing.

Isoform 3 (identifier: Q8IWQ3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     664-668: SPLSN → IIPKS
     669-736: Missing.

Isoform 4 (identifier: Q8IWQ3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     408-408: Q → QSKAMFSKSLDIAEAHPQFSKED
     647-674: DTTNCMEMMTGRLSKCGSPLSNFFDVIK → EPPPPAPGLSWGAGLKGQKVATSYESSL
     675-736: Missing.

Note: Contains a phosphoserine at position 416.

Isoform 5 (identifier: Q8IWQ3-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MTSTGKDGGAQHAQYVGPYRLEKTLGKGQT → MSPEGHPSRW...TWLCLQPSPA
     663-678: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 736	736	Serine/threonine-protein kinase BRSK2		PRO_0000085670
Regions
	Domain	19 – 270	252	Protein kinase
	Domain	297 – 339	43	UBA
	Nucleotide binding	25 – 33	9	ATP By similarity
	Motif	603 – 605	3	KEN box
	Compositional bias	424 – 468	45	Pro-rich
Sites
	Active site	141	1	Proton acceptor By similarity
	Binding site	48	1	ATP By similarity
Amino acid modifications
	Modified residue	174	1	Phosphothreonine; by LKB1 Ref.8 Ref.10
	Modified residue	260	1	Phosphothreonine; by PKA Ref.9
	Modified residue	367	1	Phosphoserine Ref.11
	Modified residue	382	1	Phosphoserine Ref.11 Ref.12
	Modified residue	393	1	Phosphoserine Ref.11 Ref.12
	Modified residue	412	1	Phosphoserine Ref.12
	Modified residue	422	1	Phosphothreonine
	Modified residue	509	1	Phosphothreonine Ref.12
Natural variations
	Alternative sequence	1 – 30	30	MTSTG…GKGQT → MSPEGHPSRWARPRRPCICP SSLCSPREPRSGPAVGRGGA AHHRVPAGHTPGPQLLQPHL HLPQGQTWLCLQPSPA in isoform 5.		VSP_022603
	Alternative sequence	408	1	Q → QSKAMFSKSLDIAEAHPQFS KED in isoform 4.		VSP_013945
	Alternative sequence	647 – 674	28	DTTNC…FDVIK → EPPPPAPGLSWGAGLKGQKV ATSYESSL in isoform 2 and isoform 4.		VSP_008154
	Alternative sequence	663 – 678	16	Missing in isoform 5.		VSP_022604
	Alternative sequence	664 – 668	5	SPLSN → IIPKS in isoform 3.		VSP_008156
	Alternative sequence	669 – 736	68	Missing in isoform 3.		VSP_008157
	Alternative sequence	675 – 736	62	Missing in isoform 2 and isoform 4.		VSP_008155
Experimental info
	Mutagenesis	48	1	K → M: Loss of catalytic activity. Causes disintegration of actin stress fibers. Ref.17 Ref.18
	Mutagenesis	174	1	T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.8 Ref.10 Ref.18
	Mutagenesis	174	1	T → E: Constitutively activated. Ref.8 Ref.10 Ref.18
	Mutagenesis	260	1	T → A: Decreased phosphorylation. Nearly abolishes stimulation of insulin secretion. Ref.9 Ref.17
	Mutagenesis	310	1	G → A: Decreased activation of kinase activity. Ref.10
	Mutagenesis	443	1	T → A: Constitutively activated. Promotes formation of actin stress fibers. Ref.17
	Sequence conflict	251	1	I → S in AAP97723. Ref.2
	Sequence conflict	251	1	I → S in AAP97724. Ref.2
	Sequence conflict	251	1	I → S in AAP97725. Ref.2
	Sequence conflict	251	1	I → S in AAP97726. Ref.2
	Sequence conflict	251	1	I → S in AAP97727. Ref.2
	Sequence conflict	251	1	I → S in AAN87839. Ref.2
	Sequence conflict	251	1	I → S in CAA07196. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: D9EBA511149449E6	FASTA	736	81,633
	10 20 30 40 50 60 MTSTGKDGGA QHAQYVGPYR LEKTLGKGQT GLVKLGVHCV TCQKVAIKIV NREKLSESVL 70 80 90 100 110 120 MKVEREIAIL KLIEHPHVLK LHDVYENKKY LYLVLEHVSG GELFDYLVKK GRLTPKEARK 130 140 150 160 170 180 FFRQIISALD FCHSHSICHR DLKPENLLLD EKNNIRIADF GMASLQVGDS LLETSCGSPH 190 200 210 220 230 240 YACPEVIRGE KYDGRKADVW SCGVILFALL VGALPFDDDN LRQLLEKVKR GVFHMPHFIP 250 260 270 280 290 300 PDCQSLLRGM IEVDAARRLT LEHIQKHIWY IGGKNEPEPE QPIPRKVQIR SLPSLEDIDP 310 320 330 340 350 360 DVLDSMHSLG CFRDRNKLLQ DLLSEEENQE KMIYFLLLDR KERYPSQEDE DLPPRNEIDP 370 380 390 400 410 420 PRKRVDSPML NRHGKRRPER KSMEVLSVTD GGSPVPARRA IEMAQHGQRS RSISGASSGL 430 440 450 460 470 480 STSPLSSPRV TPHPSPRGSP LPTPKGTPVH TPKESPAGTP NPTPPSSPSV GGVPWRARLN 490 500 510 520 530 540 SIKNSFLGSP RFHRRKLQVP TPEEMSNLTP ESSPELAKKS WFGNFISLEK EEQIFVVIKD 550 560 570 580 590 600 KPLSSIKADI VHAFLSIPSL SHSVISQTSF RAEYKATGGP AVFQKPVKFQ VDITYTEGGE 610 620 630 640 650 660 AQKENGIYSV TFTLLSGPSR RFKRVVETIQ AQLLSTHDPP AAQHLSDTTN CMEMMTGRLS 670 680 690 700 710 720 KCGSPLSNFF DVIKQLFSDE KNGQAAQAPS TPAKRSAHGP LGDSAAAGPG PGGDAEYPTG 730 KDTAKMGPPT ARREQP
	Isoform 2 [UniParc]. Checksum: E7E6704028A00876	FASTA	674	75,149
	10 20 30 40 50 60 MTSTGKDGGA QHAQYVGPYR LEKTLGKGQT GLVKLGVHCV TCQKVAIKIV NREKLSESVL 70 80 90 100 110 120 MKVEREIAIL KLIEHPHVLK LHDVYENKKY LYLVLEHVSG GELFDYLVKK GRLTPKEARK 130 140 150 160 170 180 FFRQIISALD FCHSHSICHR DLKPENLLLD EKNNIRIADF GMASLQVGDS LLETSCGSPH 190 200 210 220 230 240 YACPEVIRGE KYDGRKADVW SCGVILFALL VGALPFDDDN LRQLLEKVKR GVFHMPHFIP 250 260 270 280 290 300 PDCQSLLRGM IEVDAARRLT LEHIQKHIWY IGGKNEPEPE QPIPRKVQIR SLPSLEDIDP 310 320 330 340 350 360 DVLDSMHSLG CFRDRNKLLQ DLLSEEENQE KMIYFLLLDR KERYPSQEDE DLPPRNEIDP 370 380 390 400 410 420 PRKRVDSPML NRHGKRRPER KSMEVLSVTD GGSPVPARRA IEMAQHGQRS RSISGASSGL 430 440 450 460 470 480 STSPLSSPRV TPHPSPRGSP LPTPKGTPVH TPKESPAGTP NPTPPSSPSV GGVPWRARLN 490 500 510 520 530 540 SIKNSFLGSP RFHRRKLQVP TPEEMSNLTP ESSPELAKKS WFGNFISLEK EEQIFVVIKD 550 560 570 580 590 600 KPLSSIKADI VHAFLSIPSL SHSVISQTSF RAEYKATGGP AVFQKPVKFQ VDITYTEGGE 610 620 630 640 650 660 AQKENGIYSV TFTLLSGPSR RFKRVVETIQ AQLLSTHDPP AAQHLSEPPP PAPGLSWGAG 670 LKGQKVATSY ESSL
	Isoform 3 [UniParc]. Checksum: 2E3BE2942B8BD79B	FASTA	668	74,741
	10 20 30 40 50 60 MTSTGKDGGA QHAQYVGPYR LEKTLGKGQT GLVKLGVHCV TCQKVAIKIV NREKLSESVL 70 80 90 100 110 120 MKVEREIAIL KLIEHPHVLK LHDVYENKKY LYLVLEHVSG GELFDYLVKK GRLTPKEARK 130 140 150 160 170 180 FFRQIISALD FCHSHSICHR DLKPENLLLD EKNNIRIADF GMASLQVGDS LLETSCGSPH 190 200 210 220 230 240 YACPEVIRGE KYDGRKADVW SCGVILFALL VGALPFDDDN LRQLLEKVKR GVFHMPHFIP 250 260 270 280 290 300 PDCQSLLRGM IEVDAARRLT LEHIQKHIWY IGGKNEPEPE QPIPRKVQIR SLPSLEDIDP 310 320 330 340 350 360 DVLDSMHSLG CFRDRNKLLQ DLLSEEENQE KMIYFLLLDR KERYPSQEDE DLPPRNEIDP 370 380 390 400 410 420 PRKRVDSPML NRHGKRRPER KSMEVLSVTD GGSPVPARRA IEMAQHGQRS RSISGASSGL 430 440 450 460 470 480 STSPLSSPRV TPHPSPRGSP LPTPKGTPVH TPKESPAGTP NPTPPSSPSV GGVPWRARLN 490 500 510 520 530 540 SIKNSFLGSP RFHRRKLQVP TPEEMSNLTP ESSPELAKKS WFGNFISLEK EEQIFVVIKD 550 560 570 580 590 600 KPLSSIKADI VHAFLSIPSL SHSVISQTSF RAEYKATGGP AVFQKPVKFQ VDITYTEGGE 610 620 630 640 650 660 AQKENGIYSV TFTLLSGPSR RFKRVVETIQ AQLLSTHDPP AAQHLSDTTN CMEMMTGRLS KCGIIPKS
	Isoform 4 [UniParc]. Checksum: 857FBFE1ED9B3672	FASTA	696	77,598
	10 20 30 40 50 60 MTSTGKDGGA QHAQYVGPYR LEKTLGKGQT GLVKLGVHCV TCQKVAIKIV NREKLSESVL 70 80 90 100 110 120 MKVEREIAIL KLIEHPHVLK LHDVYENKKY LYLVLEHVSG GELFDYLVKK GRLTPKEARK 130 140 150 160 170 180 FFRQIISALD FCHSHSICHR DLKPENLLLD EKNNIRIADF GMASLQVGDS LLETSCGSPH 190 200 210 220 230 240 YACPEVIRGE KYDGRKADVW SCGVILFALL VGALPFDDDN LRQLLEKVKR GVFHMPHFIP 250 260 270 280 290 300 PDCQSLLRGM IEVDAARRLT LEHIQKHIWY IGGKNEPEPE QPIPRKVQIR SLPSLEDIDP 310 320 330 340 350 360 DVLDSMHSLG CFRDRNKLLQ DLLSEEENQE KMIYFLLLDR KERYPSQEDE DLPPRNEIDP 370 380 390 400 410 420 PRKRVDSPML NRHGKRRPER KSMEVLSVTD GGSPVPARRA IEMAQHGQSK AMFSKSLDIA 430 440 450 460 470 480 EAHPQFSKED RSRSISGASS GLSTSPLSSP RVTPHPSPRG SPLPTPKGTP VHTPKESPAG 490 500 510 520 530 540 TPNPTPPSSP SVGGVPWRAR LNSIKNSFLG SPRFHRRKLQ VPTPEEMSNL TPESSPELAK 550 560 570 580 590 600 KSWFGNFISL EKEEQIFVVI KDKPLSSIKA DIVHAFLSIP SLSHSVISQT SFRAEYKATG 610 620 630 640 650 660 GPAVFQKPVK FQVDITYTEG GEAQKENGIY SVTFTLLSGP SRRFKRVVET IQAQLLSTHD 670 680 690 PPAAQHLSEP PPPAPGLSWG AGLKGQKVAT SYESSL
	Isoform 5 [UniParc]. Checksum: B0E5187AF729E947	FASTA	766	84,832
	10 20 30 40 50 60 MSPEGHPSRW ARPRRPCICP SSLCSPREPR SGPAVGRGGA AHHRVPAGHT PGPQLLQPHL 70 80 90 100 110 120 HLPQGQTWLC LQPSPAGLVK LGVHCVTCQK VAIKIVNREK LSESVLMKVE REIAILKLIE 130 140 150 160 170 180 HPHVLKLHDV YENKKYLYLV LEHVSGGELF DYLVKKGRLT PKEARKFFRQ IISALDFCHS 190 200 210 220 230 240 HSICHRDLKP ENLLLDEKNN IRIADFGMAS LQVGDSLLET SCGSPHYACP EVIRGEKYDG 250 260 270 280 290 300 RKADVWSCGV ILFALLVGAL PFDDDNLRQL LEKVKRGVFH MPHFIPPDCQ SLLRGMIEVD 310 320 330 340 350 360 AARRLTLEHI QKHIWYIGGK NEPEPEQPIP RKVQIRSLPS LEDIDPDVLD SMHSLGCFRD 370 380 390 400 410 420 RNKLLQDLLS EEENQEKMIY FLLLDRKERY PSQEDEDLPP RNEIDPPRKR VDSPMLNRHG 430 440 450 460 470 480 KRRPERKSME VLSVTDGGSP VPARRAIEMA QHGQRSRSIS GASSGLSTSP LSSPRVTPHP 490 500 510 520 530 540 SPRGSPLPTP KGTPVHTPKE SPAGTPNPTP PSSPSVGGVP WRARLNSIKN SFLGSPRFHR 550 560 570 580 590 600 RKLQVPTPEE MSNLTPESSP ELAKKSWFGN FISLEKEEQI FVVIKDKPLS SIKADIVHAF 610 620 630 640 650 660 LSIPSLSHSV ISQTSFRAEY KATGGPAVFQ KPVKFQVDIT YTEGGEAQKE NGIYSVTFTL 670 680 690 700 710 720 LSGPSRRFKR VVETIQAQLL STHDPPAAQH LSDTTNCMEM MTGRLSKCDE KNGQAAQAPS 730 740 750 760 TPAKRSAHGP LGDSAAAGPG PGGDAEYPTG KDTAKMGPPT ARREQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[2]	Guo J.H., Yu L. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Amygdala.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 72-736 (ISOFORM 2). Tissue: Brain.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-736 (ISOFORM 2). Tissue: Eye.
[7]	"Repeat-directed isolation of a novel gene preferentially expressed from the maternal allele in human placenta." Miura K., Miyoshi O., Yun K., Inazawa J., Miyamoto T., Hayashi H., Masuzaki H., Yoshimura S., Niikawa N., Jinno Y., Ishimaru T. J. Hum. Genet. 44:1-9(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 463-736 (ISOFORM 3).
[8]	"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-174, MUTAGENESIS OF THR-174.
[9]	"BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260." Guo Z., Tang W., Yuan J., Chen X., Wan B., Gu X., Luo K., Wang Y., Yu L. Biochem. Biophys. Res. Commun. 347:867-871(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-260, MUTAGENESIS OF THR-260.
[10]	"Investigating the regulation of brain-specific kinases 1 and 2 by phosphorylation." Bright N.J., Carling D., Thornton C. J. Biol. Chem. 283:14946-14954(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-174, MUTAGENESIS OF THR-174 AND GLY-310.
[11]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-382 AND SER-393, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 (ISOFORM 4), MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-393; SER-412 AND THR-509, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP." Fogarty S., Hawley S.A., Green K.A., Saner N., Mustard K.J., Hardie D.G. Biochem. J. 426:109-118(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[14]	"Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity." Muller M., Lutter D., Puschel A.W. J. Cell Sci. 123:286-294(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its degradation in the ubiquitin-proteasome pathway." Zhou J., Wan B., Li R., Gu X., Zhong Z., Wang Y., Yu L. Biochem. Biophys. Res. Commun. 422:647-652(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COPS5, SUBCELLULAR LOCATION, UBIQUITINATION.
[16]	"BRSK2 is regulated by ER stress in protein level and involved in ER stress-induced apoptosis." Wang Y., Wan B., Li D., Zhou J., Li R., Bai M., Chen F., Yu L. Biochem. Biophys. Res. Commun. 423:813-818(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[17]	"Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta-Cells." Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W., Han X., Shi Y. J. Biol. Chem. 287:26435-26444(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PAK1, MUTAGENESIS OF LYS-48; THR-260 AND THR-443.
[18]	"Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic beta-cells." Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L., Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O., Yu L. J. Biol. Chem. 287:30368-30375(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-48 AND THR-174.
[19]	"Phosphorylation of microtubule-associated protein tau by AMPK-related kinases." Yoshida H., Goedert M. J. Neurochem. 120:165-176(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION IN MAPT PHOSPHORYLATION.
[20]	"APC/C(Cdh1) targets brain-specific kinase 2 (BRSK2) for degradation via the ubiquitin-proteasome pathway." Li R., Wan B., Zhou J., Wang Y., Luo T., Gu X., Chen F., Yu L. PLoS ONE 7:E45932-E45932(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, INTERACTION WITH FZR1, KEN BOX MOTIF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY505125 mRNA. Translation: AAS86443.1. AF533876 mRNA. Translation: AAP97723.1. AF533877 mRNA. Translation: AAP97724.1. AF533878 mRNA. Translation: AAP97725.1. AF533879 mRNA. Translation: AAP97726.1. AF533880 mRNA. Translation: AAP97727.1. AY166857 mRNA. Translation: AAN87839.1. AK131534 mRNA. Translation: BAD18671.1. AC091196 Genomic DNA. No translation available. AC136297 Genomic DNA. No translation available. AJ006701 mRNA. Translation: CAA07196.1. BC024291 mRNA. Translation: AAH24291.1. Different initiation. AF020089 mRNA. Translation: AAD09654.1. Sequence problems.
IPI	IPI00028344. IPI00339265. IPI00339266. IPI00604667. IPI00744296.
RefSeq	NP_001243556.1. NM_001256627.1. NP_001243558.1. NM_001256629.1. NP_001243559.1. NM_001256630.1. NP_003948.2. NM_003957.3.
UniGene	Hs.170819.
3D structure databases
ProteinModelPortal	Q8IWQ3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IWQ3. 1 interaction.
STRING	9606.ENSP00000310697.
PTM databases
PhosphoSite	Q8IWQ3.
Polymorphism databases
DMDM	116241272.
Proteomic databases
PaxDb	Q8IWQ3.
PRIDE	Q8IWQ3.
Protocols and materials databases
DNASU	9024.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308219; ENSP00000310697; ENSG00000174672. ENST00000308230; ENSP00000310805; ENSG00000174672. ENST00000382179; ENSP00000371614; ENSG00000174672. ENST00000526678; ENSP00000433370; ENSG00000174672. ENST00000528841; ENSP00000432000; ENSG00000174672. ENST00000529433; ENSP00000433684; ENSG00000174672. ENST00000531197; ENSP00000431152; ENSG00000174672.
GeneID	9024.
KEGG	hsa:9024.
UCSC	uc001lth.1. human. uc001lti.3. human. uc001ltj.3. human. uc001ltm.3. human. uc009ycv.1. human.
Organism-specific databases
CTD	9024.
GeneCards	GC11P001368.
H-InvDB	HIX0009361.
HGNC	HGNC:11405. BRSK2.
MIM	609236. gene.
neXtProt	NX_Q8IWQ3.
PharmGKB	PA36212.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000246447.
HOVERGEN	HBG007240.
InParanoid	Q8IWQ3.
KO	K08796.
OMA	ASSINMI.
PhylomeDB	Q8IWQ3.
Gene expression databases
ArrayExpress	Q8IWQ3.
Bgee	Q8IWQ3.
CleanEx	HS_BRSK2.
Genevestigator	Q8IWQ3.
GermOnline	ENSG00000174672. Homo sapiens.
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. [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. False negative. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8IWQ3.
ChEMBL	CHEMBL4574.
GenomeRNAi	9024.
NextBio	33809.
SOURCE	Search...

Entry information

Entry name

BRSK2_HUMAN

Accession

Primary (citable) accession number: Q8IWQ3
Secondary accession number(s): O60843 , O95099, Q5J5B4, Q6ZMQ4, Q8TB60

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.