KinaseNET

Nomenclature

Short Name:

MST3

Full Name:

Serine-threonine-protein kinase 24

Alias:

EC 2.7.11.1
MST3 isoform B
STK24
STK3
MST3b
RP11-111L24.5
Serine,threonine protein kinase 24
STE20-like kinase MST3

Classification

Type:

Protein-serine/threonine kinase

Group:

STE

Family:

STE20

SubFamily:

YSK

Specific Links

Entrez-Gene Entry:	8428
Entrez-Protein Entry:	NP_003567
GeneCards Entry:	MST3
KinBASE Entry:	MST3
OMIM Entry:	604984
Pfam Entry:	Q9Y6E0
PhosphoNET Entry:	Q9Y6E0
Phosphosite Plus Entry:	768
Protein Data Bank Entry:	2CKW
Source Entry:	STK24
UCSD-Nature Entry:	A002992
UniProt Entry:	Q9Y6E0
Kinexus Products:	MST3 Mammalian STE20-like protein-serine kinase 3; Serine-threonine-protein kinase 24 T184 phosphosite-specific antibody AB-PK727 Mammalian STE20-like protein-serine kinase 3; Serine-threonine-protein kinase 24 T190 phosphosite-specific antibody AB-PK728 Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (K187-G193, human) pT190 phosphopeptide - Powder PE-04ABJ95 Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (L181-K187, human) pT184 phosphopeptide - Powder PE-04ABK90 Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (G179-W197, human) pT182+pT184+pT190+pT194 phosphopeptide - Powder PE-04AWP75

General Links

Structure

Mol. Mass (Da):

49,308

# Amino Acids:

443

# mRNA Isoforms:

mRNA Isoforms:

49,308 Da (443 AA; Q9Y6E0); 47,913 Da (431 AA; Q9Y6E0-2)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

3CKW

Subfamily Alignment

Domain Distribution:

Start	End	Domain
36	286	Pkinase
62	89	Coiled-coil

Kinexus Products

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

hiddentext

○	Mammalian STE20-like protein-serine kinase 3; Serine-threonine-protein kinase 24 T184 phosphosite-specific antibody AB-PK727
○	Mammalian STE20-like protein-serine kinase 3; Serine-threonine-protein kinase 24 T190 phosphosite-specific antibody AB-PK728
○	Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (K187-G193, human) pT190 phosphopeptide - Powder PE-04ABJ95
○	Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (L181-K187, human) pT184 phosphopeptide - Powder PE-04ABK90
○	Mammalian STE20-like protein-serine kinase 3 / Serine-threonine-protein kinase 24 (G179-W197, human) pT182+pT184+pT190+pT194 phosphopeptide - Powder PE-04AWP75

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S49, S46, S294, S311, S315, S316, S317, S320, S434.

Threonine phosphorylated:

T18+, T182, T184+, T190+, T194-, T324.

Tyrosine phosphorylated:

Y93, Y303, Y433.

Ubiquitinated:

K44, K52, K187, K238, K292.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

32

935

45

868
11

321

20

290
100

2906

13

3094
33

953

144

1047
39

1122

36

892
14

417

117

428
33

956

43

908
49

1425

62

1540
33

950

24

640
20

591

117

1132
18

515

44

752
36

1060

227

969
31

901

46

1727
8

230

15

212
34

982

35

1582
11

325

22

304
22

634

334

2950
47

1357

24

1911
15

438

121

741
34

974

162

799
26

743

32

982
41

1184

38

1857
63

1823

16

2181
41

1198

24

1617
48

1392

32

1989
69

2016

85

2594
43

1248

49

2493
48

1386

24

1730
55

1596

24

2372
8

232

42

191
33

949

42

737
31

909

51

782
14

406

51

368
49

1427

78

834
58

1681

48

2741

Evolution

Species Conservation

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

100

100

100
99.8

100

98
39.8

58.1

98
-

-

97
-

-

96
49.7

58.8

97
-

-

-
93

94.8

98
40.3

55.8

97
-

-

-
86.5

90.5

-
39.5

57

90
39.8

55.8

88
39.2

55.7

84
-

-

-
29.3

43.8

74
-

-

-
35.6

52.9

59
-

-

-
-

-

-
-

-

-
-

-

60
-

-

-
-

-

-
-

-

61

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	STRN4 - Q9NRL3
2	STRN - O43815
3	PPP2R1A - P30153
4	MOBKL3 - Q9Y3A3
5	SLMAP - Q14BN4
6	PPP2R1B - P30154
7	FGFR1OP2 - Q9NVK5
8	PPP2CA - P67775
9	CCT8 - P50990
10	CCT2 - P78371
11	CCT7 - Q99832
12	CCT6A - P40227
13	CTTNBP2NL - Q9P2B4
14	CTTNBP2 - Q8WZ74
15	TCP1 - P17987

Regulation

Activation:

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

PKACa	P17612	T18	ALNKRRATLPHPGGS	+
MST3	Q9Y6E0	T190	DTQIKRNTFVGTPFW	+

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

MST3 (STK24)	Q9Y6E0	T190	DTQIKRNTFVGTPFW	+
NDR2 (STK38L)	Q9Y2H1	T442	DWVFLNYTYKRFEGL	+

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 2 known protein substrate phosphosites and 31 peptides phosphorylated by recombinant MST3 in vitro tested in-house by Kinexus.

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

Bosutinib	IC50 = 3.9 nM	5328940	288441	19039322
Neratinib	Kd = 6.5 nM	9915743	180022	22037378
Cdk1/2 Inhibitor III	IC50 < 25 nM	5330812	261720	22037377
Hesperadin	Kd < 50 nM	10142586	514409	19035792
PF-03814735	IC50 < 50 nM	49830590		20354118
PKR Inhibitor	IC50 > 50 nM	6490494	235641	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
Sunitinib	Kd = 63 nM	5329102	535	18183025
AT9283	IC50 > 100 nM	24905142		19143567
Lestaurtinib	Kd = 100 nM	126565		18183025
SU14813	Kd = 100 nM	10138259	1721885	18183025
TTT-3002	IC50 = 100 nM
Nintedanib	Kd = 110 nM	9809715	502835	22037378
Staurosporine	Kd = 120 nM	5279		18183025
JAK3 Inhibitor VI	IC50 > 150 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 > 150 nM	3813	281948	22037377
SU11652	IC50 > 150 nM	24906267	13485	22037377
JNJ-7706621	Kd = 180 nM	5330790	191003	18183025
Gö6983	IC50 > 250 nM	3499	261491	22037377
N-Benzoylstaurosporine	IC50 > 250 nM	56603681	608533	22037377
Dovitinib	Kd = 430 nM	57336746		18183025
AG-E-60384	IC50 = 500 nM	6419741	413188	22037377
Bisindolylmaleimide I	IC50 = 500 nM	2396	7463	22037377
IDR E804	IC50 = 500 nM	6419764	1802727	22037377
IKK-2 Inhibitor IV	IC50 = 500 nM	9903786	257167	22037377
PKCb Inhibitor	IC50 = 500 nM	6419755	366266	22037377
RGB-286147	IC50 = 500 nM	9549301	258721	22037377
SU11274	IC50 = 500 nM	9549297	261641	22037377
SU6656	IC50 = 500 nM	5353978	605003	22037377
SU9516	IC50 = 500 nM	5289419	258805	22037377
PP121	IC50 < 750 nM	24905142		18849971
HG-9-91-01	IC50 < 800 nM
A 443654	IC50 < 1 µM	10172943	379300	19465931
Alsterpaullone	IC50 > 1 µM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 1 µM	16760286	260138	22037377
Bisindolylmaleimide IV	IC50 > 1 µM	2399	266487	22037377
Gö6976	IC50 > 1 µM	3501	302449	22037377
GSK-3 Inhibitor XIII	IC50 > 1 µM	6419766	359482	22037377
Icotinib	IC50 > 1 µM	22024915		22112293
Indirubin-3′-monoxime	IC50 > 1 µM	5326739		22037377
MK5108	IC50 > 1 µM	24748204		20053775
Ro-32-0432	IC50 > 1 µM	127757	26501	22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
KW2449	Kd = 1.1 µM	11427553	1908397	22037378
AC1NS4N8	Kd < 1.25 µM	5353854	101797	19035792
AST-487	Kd = 1.3 µM	11409972	574738	22037378
Momelotinib	IC50 > 2 µM	25062766		19295546
Pelitinib	Kd = 2.1 µM	6445562	607707	18183025
NVP-TAE684	Kd = 2.9 µM	16038120	509032	22037378
Tozasertib	Kd = 3.6 µM	5494449	572878	18183025
JNJ-28871063	IC50 > 4 µM	17747413		17975007
BMS-690514	Kd < 4.5 µM	11349170		21531814

Disease Linkage

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: Bladder carcinomas (%CFC= +129, p<0.003); Brain glioblastomas (%CFC= +105, p<0.003); and Large B-cell lymphomas (%CFC= +98, p<0.09). The COSMIC website notes an up-regulated expression score for MST3 in diverse human cancers of 707, which is 1.5-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 273 for this protein kinase in human cancers was 4.6-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice support 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: 0.07 % in 25371 diverse cancer specimens. This rate is the same as 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: 0.45 % in 603 endometrium cancers tested; 0.44 % in 864 skin cancers tested; 0.35 % in 65 Meninges cancers tested; 0.3 % in 1270 large intestine cancers tested; 0.27 % in 589 stomach cancers tested; 0.13 % in 710 oesophagus cancers tested; 0.11 % in 1634 lung cancers tested; 0.09 % in 1276 kidney cancers tested; 0.08 % in 548 urinary tract cancers tested; 0.04 % in 1512 liver cancers tested; 0.03 % in 891 ovary cancers tested; 0.03 % in 1490 breast cancers tested; 0.03 % in 1467 pancreas cancers tested; 0.02 % in 939 prostate cancers tested; 0.01 % in 2082 central nervous system cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.

Frequency of Mutated Sites:

None > 3 in 20,655 cancer specimens

Comments:

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

STK24

OMIM Entry:

604984

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

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

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: