KinaseNET

Nomenclature

Short Name:

MNK2

Full Name:

MAP kinase-interacting serine-threonine kinase 2

Alias:

EC 2.7.11.1
GPRK7
GPRK8
MKNK2

Classification

Type:

Protein-serine/threonine kinase

Group:

CAMK

Family:

MAPKAPK

SubFamily:

MNK

Specific Links

BioCarta Entry:	erk pathway
Entrez-Gene Entry:	2872
Entrez-Protein Entry:	NP_060042
GeneCards Entry:	MNK2
KinBASE Entry:	MNK2
OMIM Entry:	605069
Pfam Entry:	Q9HBH9
PhosphoNET Entry:	Q9HBH9
Phosphosite Plus Entry:	725
Protein Data Bank Entry:	2AC3
Source Entry:	MKNK2
UCSD-Nature Entry:	A001555
UniProt Entry:	Q9HBH9

General Links

Structure

Mol. Mass (Da):

46711

# Amino Acids:

414

# mRNA Isoforms:

mRNA Isoforms:

51,875 Da (465 AA; Q9HBH9); 46,711 Da (414 AA; Q9HBH9-2)

4D Structure:

Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2. Also binds to dephosphorylated ERK1 and ERK2. Isoform 2 interacts with ESR2.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2AC3

Subfamily Alignment

Domain Distribution:

Start	End	Domain
84	368	Pkinase

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S15, S74, S76+, S437, S440, S442, S452.

Threonine phosphorylated:

T72+, T244+, T249+, T379+.

Ubiquitinated:

K326.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

52

1247

22

802
42

1009

15

726
16

380

13

437
28

675

88

1248
60

1446

27

713
38

903

46

641
49

1185

36

782
36

874

39

1020
49

1178

13

685
17

418

97

288
18

426

33

382
35

845

140

863
18

443

24

284
23

553

12

456
30

712

32

595
27

638

14

471
11

261

264

372
35

844

23

729
100

2397

82

1540
63

1504

87

696
10

239

29

267
32

757

32

785
18

424

14

363
24

580

23

611
21

494

30

517
61

1473

59

1313
35

847

30

572
31

741

23

702
18

429

24

416
48

1153

28

789
54

1288

18

367
49

1164

26

1012
32

776

109

1308
52

1238

52

697
14

339

44

406

Evolution

Species Conservation

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

100

100

100
42.9

48.6

96
92.4

93.5

99
-

-

95
-

-

96
34.7

36.9

92
-

-

-
92.7

95.3

95
92.7

95.3

94
-

-

-
-

-

-
60.8

73

84
76.9

87.8

78.5
73.3

84.5

79
-

-

-
24

31

-
49.8

66.7

-
-

-

50
48.7

64.6

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	MAPK1 - P28482
2	EIF4E - P06730
3	EIF4G1 - Q04637
4	ESR2 - Q92731
5	ESR1 - P03372
6	MAPK14 - Q16539
7	EIF4G2 - P78344

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

ERK2	P28482	T244	GDCSPISTPELLTPC	+
p38a	Q16539	T244	GDCSPISTPELLTPC	+
ERK1	P27361	T244	GDCSPISTPELLTPC	+
ERK2	P28482	T249	ISTPELLTPCGSAEY	+
p38a	Q16539	T249	ISTPELLTPCGSAEY	+
ERK1	P27361	T249	ISTPELLTPCGSAEY	+
ERK2	P28482	T379	APENTLPTPMVLQRN	+
p38a	Q16539	T379	APENTLPTPMVLQRN	+
ERK1	P27361	T379	APENTLPTPMVLQRN	+

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

eIF4E

P07630

S209

DTATKSGSTTKNRFV

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

Lestaurtinib	Kd = 1.4 nM	126565		22037378
AST-487	Kd = 3 nM	11409972	574738	18183025
Foretinib	Kd = 3.7 nM	42642645	1230609	22037378
BX795	IC50 = 10 nM	10077147	577784
Staurosporine	Kd = 17 nM	5279		18183025
K-252a; Nocardiopsis sp.	IC50 < 25 nM	3813	281948	22037377
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
TTT-3002	IC50 < 40 nM
NVP-TAE684	Kd = 44 nM	16038120	509032	22037378
SB218078	IC50 > 50 nM	447446	289422	22037377
Gö6976	IC50 < 80 nM	3501	302449
(5Z)-7-Oxozeaenol	IC50 = 100 nM		1077979
7-hydroxystaurosporine	IC50 > 100 nM	72271	1236539
AT9283	IC50 > 100 nM	24905142		19143567
Sorafenib	Kd = 130 nM	216239	1336	18183025
Cdk1/2 Inhibitor III	IC50 > 150 nM	5330812	261720	22037377
CHEMBL1651521	IC50 = 150 nM	53324451	1651521
Flt-3 Inhibitor III	IC50 > 150 nM	11772958		22037377
Gö6976	IC50 > 150 nM	3501	302449	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
WHI-P154	IC50 > 150 nM	3795	473773	22037377
PHA-767491	IC50 = 171 nM	11715767	225519	20722422
Aurora A Inhibitor 1 (DF)	Kd < 200 nM			21992004
Aurora A Inhibitor 23 (DF)	Kd < 200 nM			21992004
Ruxolitinib	Kd = 200 nM	25126798	1789941	22037378
AG-E-60384	IC50 > 250 nM	6419741	413188	22037377
AG1478	IC50 > 250 nM	2051	7917	22037377
ALX-270-403-M001	IC50 > 250 nM			22037377
BPIQ-I	IC50 > 250 nM	2427		22037377
Compound 56	IC50 > 250 nM	2857	29197	22037377
PD158780	IC50 > 250 nM	4707	53753	22037377
Rho Kinase Inhibitor III; Rockout	IC50 > 250 nM	644354	380071	22037377
VEGFR2 Kinase Inhibitor IV	IC50 > 250 nM	5329468	92461	22037377
Linifanib	Kd = 270 nM	11485656	223360	18183025
Gefitinib	Kd = 360 nM	123631	939	15711537
TG101348	Kd = 380 nM	16722836	1287853	22037378
Amgen TBK 1 inhibitor (Compound II)	IC50 < 400 nM
GSK650394A	IC50 < 400 nM	25022668	558642
HG-10-102-01	IC50 < 400 nM
KT5720	IC50 < 400 nM	3844	608532
BMS-777607	IC50 = 450 nM	24794418		19260711
AS601245	IC50 = 500 nM	11422035	191384	22037377
Flt-3 Inhibitor II	IC50 = 500 nM	11601743	377193	22037377
Src Kinase Inhibitor I	IC50 = 500 nM	1474853	97771	22037377
TBCA	IC50 = 500 nM	1095828		22037377
A 443654	IC50 > 600 nM	10172943	379300
Aurora A Inhibitor 29 (DF)	Kd < 600 nM			21992004
BX517	IC50 > 600 nM	11161844	228654
Novartis 12a (PKD1)	IC50 < 800 nM
R406	IC50 < 800 nM	11984591
PP242	Kd = 820 nM	25243800		22037378
CP724714	Kd = 840 nM	9874913	483321	18183025
N-Benzoylstaurosporine	Kd = 950 nM	56603681	608533	18183025
1;9-Pyrazoloanthrone	Kd = 1 µM	8515	7064	15711537
BCP9000906	IC50 > 1 µM	5494425	21156	22037377
BML-275	IC50 = 1 µM	11524144	478629
Erlotinib	Kd = 1 µM	176870	553	22037378
GSK-3 Inhibitor IX	IC50 = 1 µM	5287844	409450
GSK-3 Inhibitor X	IC50 > 1 µM	6538818	430226	22037377
GSK-3b Inhibitor XI	IC50 > 1 µM	10020713	272629	22037377
HDS029	IC50 > 1 µM	11566580	203644	22037377
Hypothemycin	IC50 = 1 µM	5477775	471474
IKK-3 inhibitor IX	IC50 = 1 µM	11626927	373751
K00596a	IC50 = 1 µM	9549298	200027
LDN193189	IC50 = 1 µM	25195294	513147
MK5108	IC50 > 1 µM	24748204		20053775
MNK1 Inhibitor	IC50 = 1 µM	11644425	1240885
MRT67307	IC50 = 1 µM	44464263
PD174265	IC50 > 1 µM	4709	188762	22037377
PF-3644022	IC50 = 1 µM
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
STO609	IC50 > 1 µM	51371511		22037377
SureCN3470757	IC50 = 1 µM	11588244	375236
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Doramapimod	Kd = 1.1 µM	156422	103667	15711537
Barasertib	Kd = 1.2 µM	16007391	215152	22037378
KW2449	Kd = 1.2 µM	11427553	1908397	22037378
CHEMBL511337	Kd = 1.23 µM	44588220	511337	19035792
Hesperadin	Kd < 1.25 µM	10142586	514409	19035792
LKB1(AAK1 dual inhibitor)	Kd < 1.25 µM	44588117	516312	19035792
Canertinib	Kd = 1.3 µM	156414	31965	15711537
Afatinib	Kd = 1.6 µM	10184653	1173655	22037378
Tofacitinib	Kd = 1.6 µM	9926791	221959	22037378
Vandetanib	Kd = 1.7 µM	3081361	24828	18183025
Vemurafenib	IC50 = 1.717 µM	42611257	1229517	20823850
Alvocidib	Kd = 1.9 µM	9910986	428690	15711537
SureCN373973	Kd < 2.5 µM	9818573	30678	19035792
SureCN7685369	Kd < 2.5 µM	9925594	526901	19035792
Quizartinib	Kd = 2.6 µM	24889392	576982	19654408
GW441756 hydrochloride	IC50 > 3 µM	16219400
H-1152; Glycyl	IC50 > 3 µM	16760635
JNKIN8	IC50 > 3 µM	57340686
A674563	Kd = 3.4 µM	11314340	379218	22037378
BMS-690514	Kd < 4 µM	11349170		21531814
FMK	IC50 > 4 µM	5737
JNJ-28871063	IC50 > 4 µM	17747413		17975007
AC1NS7CD	Kd = 4.3 µM	5329665	295136	22037378
SNS032	Kd = 4.3 µM	3025986	296468	22037378

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: Barrett's esophagus epithelial metaplasia (%CFC= -57, p<(0.0003); Bladder carcinomas (%CFC= +102, p<0.005); Brain glioblastomas (%CFC= -48, p<0.0002); Breast epithelial cell carcinomas (%CFC= +45, p<0.014); Large B-cell lymphomas (%CFC= +128, p<0.038); Oral squamous cell carcinomas (OSCC) (%CFC= -51, p<0.045); Prostate cancer - primary (%CFC= +174, p<0.0001); and Skin fibrosarcomas (%CFC= -70). The COSMIC website notes an up-regulated expression score for MNK2 in diverse human cancers of 364, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 37 for this protein kinase in human cancers was 0.6-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. Phosphorylation of MNK2 can be reduced with a D228G mutation. Kinase phosphotransferase activity can be inhibited with the T244A + T249A mutations. A T379D mutation can induce constitutive MNK2 activation.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 25371 diverse cancer specimens. This rate is only -26 % 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: 0.29 % in 589 stomach cancers tested; 0.27 % in 1270 large intestine cancers tested; 0.17 % in 864 skin cancers tested; 0.09 % in 273 cervix cancers tested; 0.09 % in 1316 breast cancers tested; 0.08 % in 603 endometrium cancers tested; 0.08 % in 1512 liver cancers tested; 0.07 % in 1956 lung cancers tested; 0.06 % in 1276 kidney cancers tested; 0.05 % in 1467 pancreas cancers tested; 0.04 % in 548 urinary tract cancers tested; 0.03 % in 958 upper aerodigestive tract cancers tested; 0.03 % in 939 prostate cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 2082 central nervous system cancers tested.

Frequency of Mutated Sites:

None > 3 in 20,654 cancer specimens

Comments:

No deletions, insertions or complex mutations are noted on the COSMIC website.

COSMIC Entry:

MKNK2_ENST00000250896

OMIM Entry:

605069

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:

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: