KinaseNET

Nomenclature

Short Name:

ZC3

Full Name:

Mitogen-activated protein kinase kinase kinase kinase 6

Alias:

B55
MINK1
Misshapen/NIK-related kinase
Misshapen-like kinase 1
YSK2
EC 2.7.11.1
Kinase MINK
MAP4K6
MINK

Classification

Type:

Protein-serine/threonine kinase

Group:

STE

Family:

STE20

SubFamily:

MSN

Specific Links

Entrez-Gene Entry:	50488
Entrez-Protein Entry:	NP_056531
GeneCards Entry:	MINK
Pfam Entry:	Q8N4C8
PhosphoNET Entry:	Q8N4C8
Phosphosite Plus Entry:	723
ScanSite Entry:	Q8N4C8
Source Entry:	MINK1
UniProt Entry:	Q8N4C8

General Links

Structure

Mol. Mass (Da):

149822

# Amino Acids:

1332

# mRNA Isoforms:

mRNA Isoforms:

149,822 Da (1332 AA; Q8N4C8); 147,653 Da (1312 AA; Q8N4C8-4); 146,711 Da (1303 AA; Q8N4C8-3); 145,806 Da (1295 AA; Q8N4C8-2); 143,637 Da (1275 AA; Q8N4C8-5)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

Subfamily Alignment

Domain Distribution:

Start	End	Domain
25	289	Pkinase
56	76	Coiled-coil
358	378	Coiled-coil
391	496	Coiled-coil
1019	1306	CNH

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K590.

Methylated:

R509.

Serine phosphorylated:

S16, S175+, S324, S326, S332, S478, S535, S601, S641, S673, S674, S699, S701, S732, S733, S747, S754, S763, S772, S773, S777, S778, S782, S903, S916, S918, S927, S939, S1088, S1317.

Threonine phosphorylated:

T59, T181+, T187+, T191-, T280, T565, T629, T644, T907, T920, T1008, T1323.

Tyrosine phosphorylated:

Y36, Y86, Y193-, Y475, Y505, Y507, Y592, Y706, Y906, Y937, Y960, Y987, Y1320.

Ubiquitinated:

K1103, K1291.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

68

721

58

838
9

99

25

86
24

251

32

273
54

571

187

619
79

841

47

683
15

161

165

233
23

250

55

434
73

784

86

1305
73

774

31

603
15

156

155

153
17

183

63

336
86

914

297

699
22

230

76

271
14

150

18

203
11

114

23

128
19

208

29

185
41

441

163

2669
16

170

45

173
9

93

173

74
63

670

215

652
49

522

47

612
21

228

55

233
28

297

36

304
18

189

45

227
19

201

47

212
94

1006

121

1723
20

215

79

259
19

203

45

183
20

218

45

223
26

279

56

173
40

430

36

393
93

987

66

858
15

155

106

269
100

1067

104

732
8

81

70

86

Evolution

Species Conservation

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

100

100

100
99.4

99.6

100
-

-

98
-

-

97.5
-

-

97
-

-

95
-

-

-
94.4

95.8

97
24.1

38.9

97
-

-

-
-

-

-
-

-

-
-

-

86
-

-

-
-

-

-
-

-

-
-

-

-
46.1

59

43
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	NCK1 - P16333
2	RAP2A - P10114
3	CALM1 - P62158
4	MAP1B - P46821
5	SPTBN2 - O15020
6	NEFM - P07197
7	YWHAZ - P63104

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

ZC3	Q8N4C8	T187	RTVGRRNTFIGTPYW	+
ZC3	Q8N4C8	T191	RRNTFIGTPYWMAPE	-
ZC3	Q8N4C8	Y193	NTFIGTPYWMAPEVI	-
CHK1	O14757	T280	TYLSRPPTEQLLKFP

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

ZC3 (MINK)	Q8N4C8	T187	RTVGRRNTFIGTPYW	+
ZC3 (MINK)	Q8N4C8	T191	RRNTFIGTPYWMAPE	-
ZC3 (MINK)	Q8N4C8	Y193	NTFIGTPYWMAPEVI	-

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

N-Benzoylstaurosporine	Kd = 170 pM	56603681	608533	19654408
Staurosporine	IC50 = 490 pM	5279		19397322
TTT-3002	IC50 < 2 nM
Bosutinib	Kd = 3.2 nM	5328940	288441	22037378
Lestaurtinib	Kd = 3.6 nM	126565		22037378
AST-487	Kd = 7.8 nM	11409972	574738	22037378
Dovitinib	Kd = 9.1 nM	57336746		22037378
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
KW2449	Kd = 25 nM	11427553	1908397	22037378
SB218078	IC50 < 25 nM	447446	289422	22037377
SU11652	IC50 < 25 nM	24906267	13485	22037377
Neratinib	Kd = 29 nM	9915743	180022	22037378
Sunitinib	Kd = 29 nM	5329102	535	22037378
Doramapimod	IC50 = 40 nM	156422	103667	22014550
Wyeth PDK1 Inhibitor Compound 1	IC50 < 40 nM
Flt-3 Inhibitor II	IC50 > 50 nM	11601743	377193	22037377
SU14813	Kd = 69 nM	10138259	1721885	22037378
Nintedanib	Kd = 82 nM	9809715	502835	22037378
A674563	Kd = 100 nM	11314340	379218	22037378
AT9283	IC50 > 100 nM	24905142		19143567
BI-D1870	IC50 < 100 nM	25023738	573107
BMS-690514	Kd < 100 nM	11349170		21531814
IKK-3 inhibitor IX	IC50 < 100 nM	11626927	373751
IPA-3	IC50 < 100 nM	521106	472940
PP242	IC50 = 100 nM	25243800
R406	IC50 = 100 nM	11984591
Ro-31-8220	IC50 < 100 nM	5083	6291
Staurosporine aglycone	IC50 < 100 nM	3035817	281948
Syk Inhibitor	IC50 = 100 nM	6419747	104279
Alsterpaullone	IC50 > 150 nM	5005498	50894	22037377
IDR E804	IC50 > 150 nM	6419764	1802727	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
PKR Inhibitor; Negative Control	IC50 > 150 nM	16760619		22037377
VEGFR2 Kinase Inhibitor II	IC50 > 150 nM	5329155	88606	22037377
Syk Inhibitor IV	IC50 = 200 nM	10200390
Alsterpaullone; 2-Cyanoethyl	IC50 > 250 nM	16760286	260138	22037377
Flt-3 Inhibitor III	IC50 > 250 nM	11772958		22037377
GSK-3 Inhibitor XIII	IC50 > 250 nM	6419766	359482	22037377
Kenpaullone	IC50 > 250 nM	3820	296586	22037377
PHA-665752	Kd = 250 nM	10461815	450786	22037378
TWS119	IC50 > 250 nM	9549289	405759	22037377
Brivanib	Kd = 310 nM	11234052	377300	22037378
Ruboxistaurin	Kd = 310 nM	153999	91829	22037378
NVP-TAE684	Kd = 330 nM	16038120	509032	22037378
A-83-01	IC50 < 400 nM	16218924	1170377
BML-275	IC50 < 400 nM	11524144	478629
GSK650394A	IC50 < 400 nM	25022668	558642
HG-9-91-01	IC50 < 400 nM
LDN193189	IC50 < 400 nM	25195294	513147
Novartis 12a (PKD1)	IC50 < 400 nM
Dasatinib	Kd = 430 nM	11153014	1421	22037378
AG-E-60384	IC50 = 500 nM	6419741	413188	22037377
ALX-270-403-M001	IC50 = 500 nM			22037377
BCP9000906	IC50 = 500 nM	5494425	21156	22037377
GSK-3 Inhibitor IX	IC50 = 500 nM	5287844	409450	22037377
Indirubin-3′-monoxime	IC50 = 500 nM	5326739		22037377
Cediranib	Kd = 540 nM	9933475	491473	22037378
Axitinib	Kd = 560 nM	6450551	1289926	22037378
IRAK-4 kinase inhibitor a	IC50 < 600 nM
Vemurafenib	IC50 < 600 nM	42611257	1229517
Momelotinib	IC50 < 750 nM	25062766		19295546
K00596a	IC50 < 800 nM	9549298	200027
KIN 112	IC50 < 800 nM
Semaxinib	IC50 < 800 nM	5329098	276711
1;9-Pyrazoloanthrone	IC50 > 1 µM	8515	7064	22037377
A 443654	IC50 < 1 µM	10172943	379300	19465931
Akt Inhibitor VIII	IC50 = 1 µM	10196499	258844
Amgen TBK 1 inhibitor (Compound II)	IC50 = 1 µM
Chelerythrine	IC50 = 1 µM	72311
Curcumin	IC50 = 1 µM	5281767	116438
GDC0879	Kd = 1 µM	11717001	525191	22037378
GW 843682X	IC50 = 1 µM	9826308	514499
GW441756 hydrochloride	IC50 = 1 µM	16219400
IKK-2 Inhibitor IV	IC50 > 1 µM	9903786	257167	22037377
Imatinib	IC50 = 1 µM	123596	941
IRAK-4 kinase inhibitor b	IC50 = 1 µM
LY364947	IC50 = 1 µM	447966	261454
MK5108	IC50 > 1 µM	24748204		20053775
Quercetagetin	IC50 = 1 µM	5281680	413552
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	24788740		18678489
SU11274	IC50 > 1 µM	9549297	261641	22037377
SU6656	IC50 = 1 µM	5353978	605003
SU9516	IC50 > 1 µM	5289419	258805	22037377
Syk Inhibitor II	IC50 = 1 µM	16760670
VEGFR2 Kinase Inhibitor IV	IC50 > 1 µM	5329468	92461	22037377
WHI-P154	IC50 > 1 µM	3795	473773	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Tozasertib	Kd = 1.1 µM	5494449	572878	22037378
Alvocidib	Kd = 1.3 µM	9910986	428690	22037378
Erlotinib	Kd = 1.3 µM	176870	553	22037378
BI2536	Kd = 1.6 µM	11364421	513909	22037378
Gefitinib	Kd = 1.8 µM	123631	939	22037378
Princeton's TrkA inhibitor compound 20h	IC50 < 2 µM
Canertinib	Kd = 2.1 µM	156414	31965	22037378
Foretinib	Kd = 2.6 µM	42642645	1230609	22037378
BI-78D3	IC50 > 3 µM	2747117	508280
BX795	IC50 > 3 µM	10077147	577784
JNKIN7	IC50 > 3 µM	57340685
Vandetanib	Kd = 3.4 µM	3081361	24828	22037378
Enzastaurin	Kd = 3.5 µM	176167	300138	22037378
AG1478	IC50 < 4 µM	2051	7917
JNJ-28871063	IC50 > 4 µM	17747413		17975007
PLX4720	IC50 < 4 µM	24180719	1230020
Torin1	IC50 < 4 µM	49836027	1255226
Crizotinib	Kd = 4.4 µM	11626560	601719	22037378
GDC-0941	IC50 > 4.5 µM	17755052	521851
GSK269962A	IC50 > 4.5 µM	16095342	220241
GSK429286	IC50 > 4.5 µM	11373846	375312
GSK461364A	IC50 > 4.5 µM	15983966	1908394
JNKIN8	IC50 > 4.5 µM	57340686
Purvalanol A	IC50 > 4.5 µM	456214	23327
Purvalanol B	IC50 > 4.5 µM	448991	23254

Disease Linkage

Comments:

ZC3 may be a tumour requiring protein (TRP), since it undergoes fewer mutations than the typical protein in cancer cells.

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: Classical Hodgkin lymphomas (%CFC= +64, p<0.013); Large B-cell lymphomas (%CFC= +67, p<0.024); Oral squamous cell carcinomas (OSCC) (%CFC= -49, p<0.011); Ovary adenocarcinomas (%CFC= +90, p<0.051); and Skin melanomas - malignant (%CFC= -57, p<0.045).

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: 0.04 % in 24434 diverse cancer specimens. This rate is -41 % 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: 0.23 % in 1052 large intestine cancers tested; 0.22 % in 805 skin cancers tested; 0.15 % in 602 endometrium cancers tested; 0.15 % in 555 stomach cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: V298G (5).

Comments:

Only 5 deletions, 2 insertions and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

MINK1_ENST00000355280

OMIM Entry:

609426

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:

Subfamily Alignment

Domain Distribution:

Post-translation Modifications

Acetylated:

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

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: