KinaseNET

Nomenclature

Short Name:

JNK2

Full Name:

Mitogen-activated protein kinase 9

Alias:

C-Jun N-terminal kinase 2
EC 2.7.11.24
MAPK9
MK09
P54a
p54aSAPK; PRKM9; Stress-activated protein kinase JNK2; JNK2A, JNK2alpha; JNK2B, JNK2beta
JNK2-alpha-2
JNK-55
Jun kinase
Kinase JNK2

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

MAPK

SubFamily:

JNK

Specific Links

Entrez-Gene Entry:	5601
Entrez-Protein Entry:	NP_002743
GeneCards Entry:	JNK2
KinBASE Entry:	JNK2
OMIM Entry:	602896
Pfam Entry:	P45984
PhosphoNET Entry:	P45984
Phosphosite Plus Entry:	1234
Protein Data Bank Entry:	3E 70
ScanSite Entry:	P45984
Source Entry:	MAPK9
UCSD-Nature Entry:	A001297
UniProt Entry:	P45984
Kinexus Products:	JNK2 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-2 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-3 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-4 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (L274-K288, human) peptide - Powder PE-01AXN99 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (V372-T386, human) peptide - Powder PE-01AXO99 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (M1-V15, human) peptide - Powder PE-01AXP90 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (F180-V186, human) pT183+pY185 phosphopeptide - Powder PE-04AZT00 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (Y185-Y191, human) pY185+pT188 phosphopeptide - Powder PE-04AZU00 Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK196 JNKSubtide - JNK1 (MAPK8) protein kinase substrate peptide - Powder PE-01BHT95 JNKSelectideA - JNK1 protein kinase substrate peptide - Powder PE-14CAD90

General Links

Structure

Mol. Mass (Da):

48139

# Amino Acids:

424

# mRNA Isoforms:

mRNA Isoforms:

48,311 Da (424 AA; P45984-4); 48,139 Da (424 AA; P45984); 44,223 Da (382 AA; P45984-3); 44,051 Da (382 AA; P45984-2); 27,334 Da (242 AA; P45984-5)

4D Structure:

Interacts with MECOM By similarity. Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with NFATC4.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

E37O

Subfamily Alignment

Domain Distribution:

Start	End	Domain
26	321	Pkinase

Kinexus Products

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

hiddentext

○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-2
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-3
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK189-4
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (L274-K288, human) peptide - Powder PE-01AXN99
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (V372-T386, human) peptide - Powder PE-01AXO99
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (M1-V15, human) peptide - Powder PE-01AXP90
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (F180-V186, human) pT183+pY185 phosphopeptide - Powder PE-04AZT00
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 (Y185-Y191, human) pY185+pT188 phosphopeptide - Powder PE-04AZU00
○	Jun N-terminus protein-serine kinase (stress-activated protein kinase (SAPK)) 2 pan-specific antibody AB-NK196
○	JNKSubtide - JNK1 (MAPK8) protein kinase substrate peptide - Powder PE-01BHT95
○	JNKSelectideA - JNK1 protein kinase substrate peptide - Powder PE-14CAD90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K250.

Serine phosphorylated:

S129+, S155, S292, S311, S407.

Threonine phosphorylated:

T178+, T183+, T188-, T404.

Tyrosine phosphorylated:

Y185+, Y357.

Ubiquitinated:

K166, K250, K353.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

30

966

38

916
3

84

18

49
7

229

12

286
24

766

134

1031
28

901

35

665
2

72

89

61
10

334

45

523
28

917

54

1468
17

538

17

451
4

144

125

147
3

95

35

154
21

684

206

668
3

105

34

148
2

49

15

42
10

314

33

421
3

112

21

55
3

91

347

74
7

220

22

460
6

185

111

199
21

681

137

624
8

246

31

306
5

145

31

157
6

197

22

211
5

163

23

270
5

176

31

248
24

784

86

833
4

122

37

215
4

132

23

193
4

117

23

166
5

146

42

146
26

833

24

711
100

3218

41

6867
3

81

81

222
33

1047

83

820
3

89

48

89

Evolution

Species Conservation

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

100

100

100
42.9

57.8

100
84.7

91.5

94
-

-

99
-

-

99
99.3

100

97
-

-

-
96.7

97.4

99
98.8

98.8

99
-

-

-
97.9

99.1

-
88.9

90.1

99
79.8

87.8

-
71.7

81.8

86
-

-

-
65.1

76.2

-
-

-

-
55.7

66.5

53
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	TP53 - P04637
2	MAPK8IP3 - Q9UPT6
3	SH3BP5 - O60239
4	MAPK8IP1 - Q9UQF2
5	TOB1 - P50616
6	DUSP4 - Q13115
7	ATF2 - P15336
8	JUND - P17535
9	NFATC3 - Q12968
10	RB1 - P06400
11	IRS1 - P35568
12	MAP2K4 - P45985
13	CDC42 - P60953
14	ELK3 - P41970
15	JDP2 - Q8WYK2

Regulation

Activation:

Phosphorylation of Thr-183 and Tyr-185 by either of two dual specificity kinases, MAP2K4 and MAP2K7, increases phosphotransferase activity. Phosphorylation of Ser-129 also increases phosphotransferase activity.

Inhibition:

Inhibited by dual specificity phosphatases, such as DUSP1, which target the Thr-183 and Tyr-185 activatory phosphorylation sites.

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

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

PKCb	P05771	S129	ELDHERMSYLLYQML	+
MEK7	O14733	T183	ACTNFMMTPYVVTRY	+
MEK4	P45985	T183	ACTNFMMTPYVVTRY	+
JNK2	P45984	T183	ACTNFMMTPYVVTRY	+
MEK7	O14733	Y185	TNFMMTPYVVTRYYR	+
MEK4	P45985	Y185	TNFMMTPYVVTRYYR	+
MEK7	O14733	T404	SSMSTEQTLASDTDS
CK2a1	P68400	T404	SSMSTEQTLASDTDS
MEK7	O14733	S407	STEQTLASDTDSSLD
CK2a1	P68400	S407	STEQTLASDTDSSLD

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

APLP2	Q06481	T736	VEVDPMLTPEERHLN
APP	P05067	T743	VEVDAAVTPEERHLS
ATF2	P15336	S90	GLFNELASPFENEFK
ATF2	P15336	T69	SVIVADQTPTPTRFL	+
ATF2	P15336	T71	IVADQTPTPTRFLKN	+
Bcl-xL	Q07817	T115	LTSQLHITPGTAYQS
Bcl-xL	Q07817	T47	GTESEMETPSAINGN
Bim	O43521	S69	GPLAPPASPGPFATR
Cdc25C	P30307	S168	SEMKYLGSPITTVPK	+
CTNNB1	P35222	S191	SRHAIMRSPQMVSAI
CTNNB1	P35222	S605	LFVQLLYSPIENIQR
Doublecortin	O43602	S415	SPISTPTSPGSLRKH
Doublecortin	O43602	T402	TSSSQLSTPKSKQSP
Doublecortin	O43602	T412	SKQSPISTPTSPGSL
Elk-1	P19419	S324	RDLELPLSPSLLGGP	+
Elk-1	P19419	S383	IHFWSTLSPIAPRSP	+
Ets-2	P15036	T72	NCELPLLTPCSKAVM	+
FOXO4	P98177	T451	PIPKALGTPVLTPPT	+
FOXO4	P98177	T455	ALGTPVLTPPTEAAS	+
GR	P04150	S226	IDENCLLSPLAGEDD	-
H2AX	P16104	S139	GKKATQASQEY____
H3.2	P84228	S29	ATKAARKSAPATGGV
HSF1	Q00613	S363	DTEGRPPSPPPTSTP
JDP-2	Q8WYK2	T148	VRTDSVKTPESEGNP
JIP1	Q9UQF2	T103	LIDATGDTPGAEDDE	-
JNK2 (MAPK9)	P45984	T183	ACTNFMMTPYVVTRY	+
Jun (c-Jun)	P05412	S63	KNSDLLTSPDVGLLK	+
Jun (c-Jun)	P05412	S73	VGLLKLASPELERLI	+
MAPKAPK5	Q8IW41	T182	IDQGDLMTPQFTPYY	+
Myc	P01106	S62	LLPTPPLSPSRRSGL
Myc	P01106	S71	SRRSGLCSPSYVAVT
NFAT3	Q14934	S213	ASRFGLGSPLPSPRA	+
NFAT3	Q14934	S217	GLGSPLPSPRASPRP	+
NFAT4	Q12968	S163	SYRESSLSPSPASSI	-
NFAT4	Q12968	S165	RESSLSPSPASSISS	-
p53	P04637	S20	PLSQETFSDLWKLLP	+
p70S6K (RPS6KB1)	P23443	S434	SFEPKIRSPRRFIGS	+
PDX1	P52945	S61	LGALEQGSPPDISPY	+
PDX1	P52945	S66	QGSPPDISPYEVPPL	+
PSEN1	P49768	S319	NSKYNAESTERESQD
PSEN1	P49768	T320	SKYNAESTERESQDT
RSK1 (RPS6KA1)	Q15418	S380	HQLFRGFSFVATGLM	+
RXRa	P19793	S260	NMGLNPSSPNDPVTN	-
RXRa	P19793	S56	SPISTLSSPINGMGP
RXRa	P19793	S70	PPFSVISSPMGPHSM
RXRa	P19793	T82	HSMSVPTTPTLGFST	-
SH3BP5	O60239	S351	PGSLDLPSPVSLSEF
Shc1	P29353	S36	TPPEELPSPSASSLG	-
Tau iso8	P10636-8	S202	SGYSSPGSPGTPGSR
Tau iso8	P10636-8	T181	KTPPAPKTPPSSGEP
Tau iso8	P10636-8	T212	TPGSRSRTPSLPTPP
Tau iso8	P10636-8	T217	SRTPSLPTPPTREPK
Tau iso8	P10636-8	T231	KKVAVVRTPPKSPSS
TIF-IA	Q9NYV6	T200	IARYVPSTPWFLMPI
TOB1	P50616	S152	PASSVSSSPSPPFGH
TOB1	P50616	S154	SSVSSSPSPPFGHSA
TOB1	P50616	S164	FGHSAAVSPTFMPRS

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 64 known protein substrate phosphosites. Note that additional binding sites on JNK substrates with D motifs (consensus=R-P-t-s/r/t-L-p-L or K/r-x-s-L-s-L/i/v-s-l/p) facilitate higher selectivity for phosphorylation by this protein kinase.

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

CHEMBL451523	IC50 = 3 nM	9917045	451523	19356929
Kinome_3027	Ki = 4 nM	11640926	378627	16759099
Doramapimod	Kd = 4.6 nM	156422	103667	20655210
Kinome_3024	Ki = 9 nM	11539329	210963	16759099
Kinome_3028	Ki = 13 nM	11590363	210928	16759099
1;9-Pyrazoloanthrone	IC50 = 40 nM	8515	7064	18077363
Hesperadin	Kd < 50 nM	10142586	514409	19035792
K-252a; Nocardiopsis sp.	IC50 > 50 nM	3813	281948	22037377
p38 MAP Kinase Inhibitor	IC50 > 50 nM	4665	91730	22037377
AST-487	Kd = 56 nM	11409972	574738	18183025
SB203580	Kd = 95 nM	176155	10	15711537
7-hydroxystaurosporine	IC50 > 100 nM	72271	1236539
AT9283	IC50 > 100 nM	24905142		19143567
Staurosporine aglycone	IC50 = 100 nM	3035817	281948
TTT-3002	IC50 < 100 nM
SB202190	Kd = 120 nM	5353940	278041	15711537
SureCN5632345	Kd < 150 nM	44593646	515466	19035792
JNK Inhibitor VIII	IC50 = 160 nM	11624601	210618	16759099
AS601245	IC50 = 220 nM	11422035	191384	18077363
CHEMBL1788116	IC50 = 220 nM	11422034	1788116	15999997
KW2449	Kd = 230 nM	11427553	1908397	22037378
Linifanib	Kd = 240 nM	11485656	223360	18183025
Pyrrolo-pyrimidone; 17	IC50 = 240 nM	16119021	461140	18945615
TG101348	Kd = 240 nM	16722836	1287853	22037378
BCP9000906	IC50 > 250 nM	5494425	21156	22037377
IDR E804	IC50 > 250 nM	6419764	1802727	22037377
JNK Inhibitor IX	IC50 > 250 nM	766949	233001	22037377
ML3403	IC50 > 250 nM	6419739	111364	22037377
NVP-TAE684	Kd = 280 nM	16038120	509032	22037378
Lestaurtinib	Kd = 320 nM	126565		22037378
JNKIN7	IC50 < 400 nM	57340685
JNKIN8	IC50 < 400 nM	57340686
FR180204	IC50 = 500 nM	11493598	259551	22037377
PD169316	IC50 = 500 nM	4712	17331	22037377
PDK1/Akt/Flt Dual Pathway Inhibitor	IC50 = 500 nM	5113385	599894	22037377
PKR Inhibitor	IC50 = 500 nM	6490494	235641	22037377
GSK1838705A	Kd = 520 nM	25182616	464552	22037378
A 443654	IC50 > 600 nM	10172943	379300
CZC-25146	IC50 < 600 nM
Gö6976	IC50 > 600 nM	3501	302449
HG-9-91-01	IC50 < 600 nM
R406	IC50 < 600 nM	11984591
Foretinib	Kd = 670 nM	42642645	1230609	22037378
SPDD01923	IC50 = 675 nM	447721	305178	10377223
Momelotinib	IC50 < 750 nM	25062766		19295546
Amgen TBK 1 inhibitor (Compound II)	IC50 < 800 nM
BX517	IC50 > 900 nM	11161844	228654
Staurosporine	Kd = 910 nM	5279		22037378
AG-E-60384	IC50 > 1 µM	6419741	413188	22037377
BX795	IC50 = 1 µM	10077147	577784
GSK-3 Inhibitor IX	IC50 = 1 µM	5287844	409450
GSK650394A	IC50 = 1 µM	25022668	558642
Indirubin-3′-monoxime	IC50 > 1 µM	5326739		22037377
JAK3 Inhibitor VI	IC50 > 1 µM	16760524		22037377
MK5108	IC50 > 1 µM	24748204		20053775
NU6140	IC50 > 1 µM	10202471	1802728	22037377
PKCbII/EGFR Inhibitor	IC50 > 1 µM	6711154		22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN3470757	IC50 = 1 µM	11588244	375236
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Zearalenone	IC50 = 1 µM	5281576	454173
Canertinib	Kd = 1.1 µM	156414	31965	15711537
Gefitinib	Kd = 1.4 µM	123631	939	15711537
GDC-0941	Kd = 1.8 µM	17755052	521851	22037378
Erlotinib	Kd = 2 µM	176870	553	22037378
Pyrimidylpyrrole, 11e	Ki = 2 µM	11634725	583042	19827834
Afatinib	Kd = 2.1 µM	10184653	1173655	22037378
Sunitinib	Kd = 2.4 µM	5329102	535	22037378
SureCN7018367	Kd < 2.5 µM	18792927	450519	19035792
VX702	Kd = 2.6 µM	10341154	1090090	19950901
KT5720	IC50 > 3 µM	3844	608532
Aloisine A	IC50 = 3.3 µM	5326843	75680	12519061
SU14813	Kd = 3.3 µM	10138259	1721885	22037378
Sorafenib	Kd = 3.6 µM	216239	1336	15711537
JNJ-28871063	IC50 > 4 µM	17747413		17975007
CHEMBL590109	IC50 = 4.1 µM	46224684	590109	19926477
BMS-690514	Kd < 4.5 µM	11349170		21531814
Pyrimidone, 62	IC50 = 4.7 µM	24769780	447602	18763753

Disease Linkage

General Disease Association:

Cancer

Specific Cancer Types:

Breast cancer

Comments:

JNK2 has been shown, in a cancer cell line to have a role in breast cancer cell motility.

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 human Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +152, p<0.0001). The COSMIC website notes an up-regulated expression score for JNK2 in diverse human cancers of 563, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 230 for this protein kinase in human cancers was 3.8-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.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25492 diverse cancer specimens. This rate is very similar (+ 5% higher) 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: 0.54 % in 1093 large intestine cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: G227C (4); G35E (3).

Comments:

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

COSMIC Entry:

MAPK9_ENST00000452135

OMIM Entry:

602896

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

Acetylated:

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:

Kinections Map

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 Cancer Types:

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: