KinaseNET

Nomenclature

Short Name:

MST2

Full Name:

Serine-threonine-protein kinase 3

Alias:

EC 2.7.11.1
FLJ90748
CLIK1
Krs-1
MESS1
Serine,threonine protein kinase 3
STK3

Classification

Type:

Protein-serine/threonine kinase

Group:

STE

Family:

STE20

SubFamily:

MST

Specific Links

Entrez-Gene Entry:	6788
Entrez-Protein Entry:	NP_006272
GeneCards Entry:	MST2
KinBASE Entry:	MST2
OMIM Entry:	605030
Pfam Entry:	Q13188
PhosphoNET Entry:	Q13188
Phosphosite Plus Entry:	770
ScanSite Entry:	Q13188
Source Entry:	STK3
UCSD-Nature Entry:	A001347
UniProt Entry:	Q13188

General Links

Structure

Mol. Mass (Da):

56,301

# Amino Acids:

491

# mRNA Isoforms:

mRNA Isoforms:

59,462 Da (519 AA; Q13188-2); 56,301 Da (491 AA; Q13188)

4D Structure:

Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation By similarity. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1, which leads to enzyme activation

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

4LG4

Subfamily Alignment

Domain Distribution:

Start	End	Domain
27	278	Pkinase
287	323	Coiled-coil
437	484	SARAH

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S15, S18, S316, S323, S333, S385, S392, S444..

Threonine phosphorylated:

T117-, T172+, T174+, T180+, T235, T240, T325, T336, T384-.

Tyrosine phosphorylated:

Y81, Y396.

Ubiquitinated:

K56, K116, K148, K161, K177, K243, K298.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

72

834

29

1008
4

45

15

44
5

59

2

74
29

331

85

588
61

700

24

645
11

122

88

191
16

188

31

416
100

1155

33

2268
33

383

17

316
5

63

72

58
4

43

19

45
44

505

173

569
2

18

24

19
9

104

12

109
3

34

14

27
5

57

15

48
22

249

112

1315
2

25

10

16
4

47

77

58
48

552

109

649
4

41

13

22
3

33

16

30
2

20

20

26
3

34

11

24
1.3

15

13

17
80

922

51

1405
2

18

27

16
2

19

11

16
6

66

11

46
0.9

10

28

9
46

535

24

541
33

376

36

393
18

205

67

418
59

684

62

644
16

189

35

287

Evolution

Species Conservation

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

100

100

100
86.8

86.8

100
78.6

89.8

100
-

-

100
-

-

96
99.4

99.6

99
-

-

-
95.8

97.2

97
96.7

98.4

97
-

-

-
53.2

56.4

-
79.4

88.2

98
93.7

96.3

94
89.4

93.5

89
-

-

-
46.2

58.6

46
66.4

75.6

-
51.5

67

74
65

78.6

-
-

-

-
-

-

-
-

-

43
-

-

43
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	SAV1 - Q9H4B6
2	CASP3 - P42574
3	RAF1 - P04049
4	LATS1 - O95835

Regulation

Activation:

Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by Raf1.

Inhibition:

Inhibited by the C-terminal non-catalytic region.

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

Akt1	P31749	T117	IIRLRNkTLIEDEIA	-
MST2	Q13188	T180	DTMAKRNTVIGTPFW	+
Akt1	P31749	T384	GTMKRNATSPQVQRP	-

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

Abl1	P00519	T735	DTEWRSVTLPRDLQS	+
LATS1	O95835	S872	GDHPRQDSMDFSNEW	+
LATS1	O95835	S909	HQRCLAHSLVGTPNY	+
LATS1	O95835	T1012	KAHPFFKTIDFSSDL
LATS1	O95835	T1060	EEENVNDTLNGWYKN
LATS1	O95835	T1079	EHAFYEFTFRRFFDD	+
LATS1	O95835	T967	MKVINWQTSLHIPPQ
MOBKL1A (MOB1B)	Q7L9L4	T12	FGSRSSKTFKPKKNI	+
MOBKL1A (MOB1B)	Q7L9L4	T35	LLKHAEATLGSGNLR	+
MOBKL1B (MOB1A)	Q9H8S9	T74	QINMLYGTITEFCTE	+
MST2 (CLIK1, STK3)	Q13188	T180	DTMAKRNTVIGTPFW	+
YAP1	P46937	S127	PQHVRAHSSPASLQL

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 = 180 pM	5279		18183025
7-hydroxystaurosporine	IC50 < 2 nM	72271	1236539
Lestaurtinib	Kd = 2.4 nM	126565		22037378
TTT-3002	IC50 < 4 nM
BX517	IC50 < 8 nM	11161844	228654
AC1NS4N8	Kd < 10 nM	23649240		19035792
Hesperadin	Kd < 10 nM	10142586	514409	19035792
N-Benzoylstaurosporine	Kd = 17 nM	56603681	608533	19654408
Sunitinib	Kd = 19 nM	5329102	535	18183025
Cdk1/2 Inhibitor III	IC50 < 25 nM	5330812	261720	22037377
Gö6976	IC50 < 25 nM	3501	302449	22037377
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 < 25 nM	3813	281948	22037377
PKR Inhibitor	IC50 < 25 nM	6490494	235641	22037377
SB218078	IC50 < 25 nM	447446	289422	22037377
Nintedanib	Kd = 38 nM	9809715	502835	22037378
Gö6976	IC50 < 40 nM	3501	302449
Gö7874	IC50 < 40 nM	5327863
GSK-3 Inhibitor IX	IC50 < 40 nM	5287844	409450
Princeton's TrkA inhibitor compound 20h	IC50 < 40 nM
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
SureCN3470757	IC50 < 40 nM	11588244	375236
Wyeth PDK1 Inhibitor Compound 1	IC50 < 40 nM
BCP9000906	IC50 > 50 nM	5494425	21156	22037377
IDR E804	IC50 > 50 nM	6419764	1802727	22037377
PF-03814735	IC50 < 50 nM	49830590		20354118
SU9516	IC50 > 50 nM	5289419	258805	22037377
Neratinib	Kd = 58 nM	9915743	180022	22037378
A 443654	IC50 < 60 nM	10172943	379300
Ro-31-8220	IC50 < 60 nM	5083	6291
Syk Inhibitor	IC50 < 60 nM	6419747	104279
JNJ-7706621	Kd = 61 nM	5330790	191003	18183025
SU14813	Kd = 65 nM	10138259	1721885	18183025
LKB1(AAK1 dual inhibitor)	Kd = 75 nM	44588117	516312	19035792
Ruboxistaurin	IC50 < 80 nM	153999	91829
AT9283	IC50 > 100 nM	24905142		19143567
BI-D1870	IC50 = 100 nM	25023738	573107
CHEMBL1650545	IC50 > 100 nM	53316611	1650545	21128646
GW 843682X	IC50 = 100 nM	9826308	514499
SU6656	IC50 < 100 nM	5353978	605003
IKK-2 Inhibitor IV	Kd < 150 nM	9903786	257167	19035792
Indirubin-3′-monoxime	IC50 > 150 nM	5326739		22037377
SU11652	IC50 > 150 nM	24906267	13485	22037377
Tozasertib	Kd < 150 nM	5494449	572878	19035792
Bosutinib	IC50 = 191 nM	5328940	288441	19039322
Dovitinib	Kd = 200 nM	57336746		18183025
AG-E-60384	IC50 > 250 nM	6419741	413188	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 250 nM	16760286	260138	22037377
Bisindolylmaleimide I	IC50 > 250 nM	2396	7463	22037377
Flt-3 Inhibitor II	IC50 > 250 nM	11601743	377193	22037377
GSK-3 Inhibitor X	IC50 > 250 nM	6538818	430226	22037377
PKR Inhibitor; Negative Control	IC50 > 250 nM	16760619		22037377
PP121	IC50 < 250 nM	24905142		18849971
NVP-TAE684	Kd = 310 nM	16038120	509032	22037378
IKK-3 inhibitor IX	IC50 < 400 nM	11626927	373751
GTP-14564	IC50 = 500 nM	3385203	406375	22037377
PKCb Inhibitor	IC50 = 500 nM	6419755	366266	22037377
CHEMBL590109	= 570 nM	46224684	590109
Aurora A Inhibitor 1 (DF)	Kd < 600 nM			21992004
GSK650394A	IC50 < 600 nM	25022668	558642
KT5720	IC50 < 600 nM	3844	608532
PP242	IC50 < 600 nM	25243800
Purvalanol A	IC50 < 600 nM	456214	23327
Kinome_714	IC50 = 650 nM	46886323		20346655
CHEMBL1240703	Kd = 760 nM	52945601	1240703	19654408
1;9-Pyrazoloanthrone	IC50 < 800 nM	8515	7064
GW441756 hydrochloride	IC50 < 800 nM	16219400
GW5074 (Raf1 Kinase Inhibitor I)	IC50 < 800 nM	5924208
AST-487	Kd = 860 nM	11409972	574738	18183025
Crizotinib	Kd = 990 nM	11626560	601719	22037378
1-Naphthyl PP1	IC50 = 1 µM	4877
Alsterpaullone	IC50 = 1 µM	5005498	50894	17850214
ALX-270-403-M001	IC50 > 1 µM			22037377
Bisindolylmaleimide IV	IC50 > 1 µM	2399	266487	22037377
GSK-3 Inhibitor XIII	IC50 > 1 µM	6419766	359482	22037377
H-1152; Glycyl	IC50 = 1 µM	16760635
H-89	IC50 > 1 µM	449241	104264	22037377
Kenpaullone	IC50 = 1 µM	3820	296586
MK5108	IC50 > 1 µM	24748204		20053775
NU6140	IC50 > 1 µM	10202471	1802728	22037377
NVP-BEZ235	IC50 = 1 µM	11977753	1879463
Orantinib	IC50 = 1 µM	5329099	274654
PP1 Analog II; 1NM-PP1	IC50 = 1 µM	5154691	573578
Purvalanol B	IC50 = 1 µM	448991	23254
Quercetagetin	IC50 = 1 µM	5281680	413552
R406	IC50 = 1 µM	11984591
SB415286	IC50 < 1 µM	4210951	322970
Semaxinib	IC50 = 1 µM	5329098	276711
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN10063060	Ki > 1 µM	52936621		21391610
Syk Inhibitor II	IC50 = 1 µM	16760670
Syk Inhibitor IV	IC50 = 1 µM	10200390
VEGFR2 Kinase Inhibitor II	IC50 > 1 µM	5329155	88606	22037377
Vemurafenib	IC50 = 1 µM	42611257	1229517
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
SureCN7018367	Kd < 1.25 µM	18792927	450519	19035792
Linifanib	Kd = 1.4 µM	11485656	223360	18183025
Enzastaurin	Kd = 1.9 µM	176167	300138	22037378
PHA-665752	Kd = 1.9 µM	10461815	450786	22037378
Momelotinib	IC50 > 2 µM	25062766		19295546
SB202190	IC50 = 2 µM	5353940	278041
Axitinib	Kd = 2.2 µM	6450551	1289926	22037378
Pelitinib	Kd = 2.4 µM	6445562	607707	18183025
CHEMBL249097	Kd < 2.5 µM	25138012	249097	19035792
SureCN373973	Kd < 2.5 µM	9818573	30678	19035792
Amgen TBK 1 inhibitor (Compound II)	IC50 > 3 µM
BMS-690514	Kd < 3 µM	11349170		21531814
JNKIN7	IC50 > 3 µM	57340685
Ruxolitinib	IC50 > 3 µM	25126798	1789941
Tofacitinib	IC50 > 3 µM	9926791	221959
BX795	IC50 < 4 µM	10077147	577784
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Harmane	IC50 > 4.5 µM	5281404	12014
JNKIN8	IC50 > 4.5 µM	57340686
KIN 112	IC50 > 4.5 µM

Disease Linkage

General Disease Association:

Cancer

Comments:

MST2 might be a tumour suppressor protein (TSP). MST2 may function in a way similar to a growth suppressor. The protein is critical in organ size control and tumour suppression by restricting proliferation and promoting apoptosis. MST2 levels are up-regulated almost 3-fold higher in human cancers when compared to most other protein kinases.

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Cervical cancer (%CFC= -67, p<(0.0003); Colon mucosal cell adenomas (%CFC= +58, p<0.012); Head and neck squamous cell carcinomas (HNSCC) (%CFC= +68, p<0.005); and Oral squamous cell carcinomas (OSCC) (%CFC= +128, p<0.007). The COSMIC website notes an up-regulated expression score for MST2 in diverse human cancers of 1337, which is 2.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 76 for this protein kinase in human cancers was 1.3-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. A K56R mutation can abrogate phosphotransferase activity, and D322N substitution can produce resistant to proteolytic cleavage.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25371 diverse cancer specimens. This rate is only -6 % lower and is very similar to 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: 0.41 % in 602 endometrium cancers tested; 0.28 % in 1093 large intestine cancers tested.

Frequency of Mutated Sites:

None > 3 in 20,655 cancer specimens

Comments:

Only 3 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

STK3

OMIM Entry:

605030

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:

Post-translation Modifications

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:

Comments:

Gene Expression in Cancers:

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: