KinaseNET

Nomenclature

Short Name:

BRSK2

Full Name:

BR serine-threonine-protein kinase 2

Alias:

BR serine/threonine kinase 2
C11orf7
Serine/threonine kinase 29
Serine/threonine- protein kinase 29
STK29
EC 2.7.11.1
PEN11B
SAD1B
Serine,threonine-protein kinase 29

Classification

Type:

Protein-serine/threonine kinase

Group:

CAMK

Family:

CAMKL

SubFamily:

BRSK

Specific Links

Entrez-Gene Entry:	9024
Entrez-Protein Entry:	NP_003948
GeneCards Entry:	PEN11B
KinBASE Entry:	BRSK2
OMIM Entry:	609236
Pfam Entry:	Q8IWQ3
PhosphoNET Entry:	Q8IWQ3
Phosphosite Plus Entry:	15307
ScanSite Entry:	Q8IWQ3
Source Entry:	BRSK2
UCSD-Nature Entry:	A003618
UniProt Entry:	Q8IWQ3
Kinexus Products:	BRSK2 BrskSubtide - BRSK2 protein kinase substrate peptide - Powder PE-01BGL99

General Links

Structure

Mol. Mass (Da):

81,633

# Amino Acids:

736

# mRNA Isoforms:

mRNA Isoforms:

84,832 Da (766 AA; Q8IWQ3-5); 81,633 Da (736 AA; Q8IWQ3); 77,598 Da (696 AA; Q8IWQ3-4); 75,149 Da (674 AA; Q8IWQ3-2); 74,741 Da (668 AA; Q8IWQ3-3); 68,740 Da (614 AA; Q8IWQ3-6)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

4YOM

Subfamily Alignment

Domain Distribution:

Start	End	Domain
19	270	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	BrskSubtide - BRSK2 protein kinase substrate peptide - Powder PE-01BGL99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Methylated:

R437.

Serine phosphorylated:

S294, S367, S382, S393, S410, S412, S417, S423, S426, S427, S435, S439, S466, S481, S489, S506, S512, S513, S520.

Threonine phosphorylated:

T174+, T260+, T431, T443, T463, T509.

Tyrosine phosphorylated:

Y15.

Ubiquitinated:

K48.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

51

465

22

656
1.2

11

12

9
0.6

5

1

0
35

318

73

708
26

235

27

223
22

200

54

553
19

169

32

436
92

833

22

1227
20

181

13

219
8

73

71

196
14

131

17

328
47

428

104

471
0.2

2

12

1
1.1

10

9

5
54

487

14

1196
1.3

12

12

7
3

23

105

118
1.4

13

9

6
2

22

64

17
27

249

87

248
35

320

13

733
14

126

15

312
0.3

3

2

1
3

28

9

24
14

129

13

293
100

908

44

1809
0.9

8

18

8
1.4

13

9

6
2

15

9

9
12

105

28

116
41

371

18

270
36

326

26

423
3

26

69

128
70

640

52

567
15

132

35

219

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
0

0

92
-

-

-
-

-

97.5
-

-

-
89.8

90.3

99
-

-

-
97.9

98.7

98
25.4

43.2

98
-

-

-
-

-

-
27.4

43.9

93
-

-

86
25.1

37.9

88.5
-

-

-
50.9

63.5

63
-

-

-
23.1

37.3

65
-

-

-
-

-

-
-

-

-
-

-

-
27.8

43.2

-
22.9

33.9

39
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	CDC25B - P30305
2	CDC25C - P30307
3	WEE1 - P30291
4	NUAK1 - O60285

Regulation

Activation:

Activated by phosphorylation on Thr-174 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39.

Inhibition:

Synthesis:

Degradation:

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

LKB1	Q15831	T174	VGDSLLETSCGSPHY	+
PKACa	P17612	T260	VDAARRLTLEHIQKH	+

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

AMPKa1 (PRKAA1)	Q13131	T183	SDGEFLRTSCGSPNY	+
MAPT/TAU	P10636	S579	NVKSKIGSTENLKHQ
MAPT/TAU	P10636	T529	TPGSRSRTPSLPTPP
PCTAIRE1	Q00536	S12	KKIKRQLSMTLRGGR	?
Wee1	P30291	S642	KKMNRSVSLTIY___	-

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Staurosporine	Kd = 3.5 nM	5279		18183025
TTT-3002	IC50 < 4 nM
7-hydroxystaurosporine	IC50 < 6 nM	72271	1236539
BX517	IC50 < 6 nM	11161844	228654
Lestaurtinib	Kd = 16 nM	126565		22037378
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
SureCN3470757	IC50 < 40 nM	11588244	375236
PP242	Kd = 42 nM	25243800		22037378
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
K-252a; Nocardiopsis sp.	IC50 > 50 nM	3813	281948	22037377
PKR Inhibitor	IC50 > 50 nM	6490494	235641	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
SureCN7018367	Kd < 50 nM	18792927	450519	19035792
Hesperadin	Kd = 92 nM	10142586	514409	19035792
AT9283	IC50 > 100 nM	24905142		19143567
AZ960	IC50 < 100 nM	25099184		18775810
Gö6976	IC50 = 100 nM	3501	302449
GSK-3 Inhibitor IX	IC50 = 100 nM	5287844	409450
SU6656	IC50 = 100 nM	5353978	605003	17850214
BCP9000906	IC50 > 150 nM	5494425	21156	22037377
Gö6976	IC50 > 150 nM	3501	302449	22037377
Indirubin-3′-monoxime	IC50 > 150 nM	5326739		22037377
JAK3 Inhibitor VI	IC50 > 150 nM	16760524		22037377
N-Benzoylstaurosporine	IC50 > 150 nM	56603681	608533	22037377
NVP-TAE684	Kd = 190 nM	16038120	509032	22037378
AG-E-60384	IC50 > 250 nM	6419741	413188	22037377
Alsterpaullone	IC50 > 250 nM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 250 nM	16760286	260138	22037377
ALX-270-403-M001	IC50 > 250 nM			22037377
Flt-3 Inhibitor II	IC50 > 250 nM	11601743	377193	22037377
GSK-3 Inhibitor X	IC50 > 250 nM	6538818	430226	22037377
IDR E804	IC50 > 250 nM	6419764	1802727	22037377
Gö7874	IC50 < 400 nM	5327863
KT5720	IC50 < 400 nM	3844	608532
SU11652	IC50 = 500 nM	24906267	13485	22037377
Sunitinib	IC50 = 500 nM	5329102	535	22037377
A 443654	IC50 > 600 nM	10172943	379300
GW 843682X	IC50 < 600 nM	9826308	514499
Novartis 12a (PKD1)	IC50 < 600 nM
Amgen TBK 1 inhibitor (Compound II)	IC50 < 800 nM
Aurora A Inhibitor 23 (DF)	Kd < 800 nM			21992004
BX795	IC50 < 800 nM	10077147	577784
H-1152; Glycyl	IC50 < 800 nM	16760635
IKK-3 inhibitor IX	IC50 < 800 nM	11626927	373751
MNK1 Inhibitor	IC50 < 800 nM	11644425	1240885
PF-3644022	IC50 < 800 nM
Ro-31-8220	IC50 < 800 nM	5083	6291
Syk Inhibitor	IC50 < 800 nM	6419747	104279
1;9-Pyrazoloanthrone	IC50 = 1 µM	8515	7064
Aurora A Inhibitor 1 (DF)	Kd = 1 µM			21992004
Bisindolylmaleimide I	IC50 > 1 µM	2396	7463	22037377
BML-275	IC50 = 1 µM	11524144	478629	17850214
Doramapimod	IC50 < 1 µM	156422	103667	17850214
Dovitinib	IC50 > 1 µM	57336746		22037377
Gö6983	IC50 > 1 µM	3499	261491	22037377
GSK-3 Inhibitor XIII	IC50 > 1 µM	6419766	359482	22037377
GSK461364A	IC50 = 1 µM	15983966	1908394
K00596a	IC50 = 1 µM	9549298	200027
Kenpaullone	IC50 = 1 µM	3820	296586
MK5108	IC50 > 1 µM	24748204		20053775
Orantinib	IC50 = 1 µM	5329099	274654
PDK1/Akt/Flt Dual Pathway Inhibitor	IC50 > 1 µM	5113385	599894	22037377
PP1	IC50 < 1 µM	1400	306380
Resveratrol	IC50 = 1 µM	445154	165
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SU9516	IC50 > 1 µM	5289419	258805	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Zearalenone	IC50 = 1 µM	5281576	454173
KW2449	Kd = 1.2 µM	11427553	1908397	22037378
BMS-690514	Kd < 1.5 µM	11349170		21531814
SB415286	IC50 = 2 µM	4210951	322970
AC1O6ZUA	Kd < 2.5 µM	6539569	408019	19035792
Tozasertib	Kd < 2.5 µM	5494449	572878	19035792
JNJ-7706621	Kd = 2.7 µM	5330790	191003	18183025
FMK	IC50 = 3 µM	5737
GW441756 hydrochloride	IC50 > 3 µM	16219400
Ruboxistaurin	IC50 > 3 µM	153999	91829
CZC-25146	IC50 < 4 µM
GSK2334470	IC50 < 4 µM	46215815	1765740
GSK650394A	IC50 < 4 µM	25022668	558642
JNJ-28871063	IC50 > 4 µM	17747413		17975007
LDN193189	IC50 < 4 µM	25195294	513147
Quercetagetin	IC50 < 4 µM	5281680	413552
SU14813	Kd = 4.1 µM	10138259	1721885	18183025
JNKIN7	IC50 > 4.5 µM	57340685
JNKIN8	IC50 > 4.5 µM	57340686
MRT67307	IC50 > 4.5 µM	44464263
Wortmannin	IC50 > 4.5 µM	312145	428496

Disease Linkage

General Disease Association:

Neurological disorders

Specific Diseases (Non-cancerous):

Limbic encephalitis

Comments:

Mutations on multiple sites can be either activatory or inhibitory on BRSK2's phosphotransferase activity. Example of diseases that may be associated with BRSK2 are limbic encephalitis and small-cell lung cancer (SCLC). BRSK2 may be an autoantigen involved in the pathogenesis of SCLC-associated limbic encephalitis and SCLC patients with paraneoplastic neurological syndromes have been reported to have antibodies against BRSK2 (PubMed:16165222).

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24434 diverse cancer specimens. This rate is -40 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.31 % in 864 skin cancers tested; 0.25 % in 273 cervix cancers tested; 0.14 % in 1229 large intestine cancers tested.

Frequency of Mutated Sites:

None > 2 in 20,009 cancer specimens

Comments:

Only 3 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

BRSK2_ENST00000308219

OMIM Entry:

609236

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

Group:

Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Methylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Ubiquitinated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Binding Proteins

hiddentext

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

General Disease Association:

Specific Diseases (Non-cancerous):

Comments:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: