KinaseNET

Nomenclature

Short Name:

EPHA6

Full Name:

Ephrin type-A receptor 6 [partial]

Alias:

EC 2.7.10.1
EHK2
FLJ35246
DKFZp434C1418; PRO57066; Tyrosine-protein kinase receptor EHK-2
EPH homology kinase 2
Eph homology kinase-2
EPH receptor A6
Ephrin type-A receptor 6

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

Eph

SubFamily:

Specific Links

Entrez-Gene Entry:	285220
Entrez-Protein Entry:	NP_775926
KinBASE Entry:	EPHA6
Pfam Entry:	Q9UF33
PhosphoNET Entry:	Q9UF33
Phosphosite Plus Entry:	7487
UCSD-Nature Entry:	A000845
UniProt Entry:	Q9UF33

General Links

Structure

Mol. Mass (Da):

116,116

# Amino Acids:

1035

# mRNA Isoforms:

mRNA Isoforms:

116,379 Da (1036 AA; Q9UF33); 44,466 Da (398 AA; Q9UF33-3); 37,274 Da (334 AA; Q9UF33-2);

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

Subfamily Alignment

Domain Distribution:

Start	End	Domain
1	22	signal_peptide
34	207	EPH_lbd
268	312	GCC2_GCC3
330	434	FN3
438	533	FN3
549	571	TMD
631	930	TyrKc
960	1024	SAM
630	943	Pkinase

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K587, K588.

N-GlcNAcylated:

N343, N397, N410.

Serine phosphorylated:

S92, S93, S300, S714, S715, S807, S808, S814, S815, S819, S820.

Threonine phosphorylated:

T88, T89, T663, T664.

Tyrosine phosphorylated:

Y787, Y788, Y793, Y794, Y849, Y850.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

38

1443

15

1235
0.3

13

2

7
-

-

-

-
0.5

19

46

11
10

380

17

180
0.2

6

18

6
0.1

5

20

4
-

-

-

-
-

-

-

-
1

45

24

32
-

-

-

-
11

419

23

409
-

-

-

-
-

-

-

-
-

-

-

-
0.1

5

10

5
0.2

7

8

4
-

-

-

-
2

64

18

29
10

394

51

180
-

-

-

-
-

-

-

-
-

-

-

-
-

-

-

-
-

-

-

-
13

482

32

402
-

-

-

-
-

-

-

-
-

-

-

-
1

39

14

34
-

-

-

-
100

3830

22

5415
2

63

53

208
14

550

52

481
4

160

44

270

Evolution

Species Conservation

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

100

100

100
40.2

58.9

99
98.8

99.4

99.5
-

-

97
-

-

-
87

89.2

99
-

-

-
96.6

98.2

95
95.8

97.6

95
-

-

-
89.4

93

-
61.5

76.1

92
58.2

72

86
56.2

70.3

79
-

-

-
-

-

34
-

-

-
-

-

30
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	MLLT4 - P55196

Regulation

Activation:

Activated by binding ephrin-A1, A2, A3, A4 or A5.

Inhibition:

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

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

Foretinib	Kd = 1.1 nM	42642645	1230609	22037378
Hesperadin	Kd < 10 nM	10142586	514409	19035792
CHEMBL249097	Kd = 20 nM	25138012	249097	19035792
Bosutinib	IC50 < 25 nM	5328940	288441	22037377
Cediranib	Kd = 36 nM	9933475	491473	22037378
PP1 Analog II; 1NM-PP1	IC50 > 50 nM	5154691	573578	22037377
Vandetanib	Kd = 50 nM	3081361	24828	18183025
Crizotinib	Kd = 65 nM	11626560	601719	22037378
Canertinib	Kd = 72 nM	156414	31965	15711537
NVP-TAE684	Kd = 120 nM	16038120	509032	22037378
R406	Kd = 120 nM	11984591		22037378
AG1478	IC50 > 150 nM	2051	7917	22037377
SU11274	IC50 > 150 nM	9549297	261641	22037377
Brivanib	Kd = 190 nM	11234052	377300	22037378
Sorafenib	Kd = 240 nM	216239	1336	15711537
Staurosporine	Kd = 240 nM	5279		15711537
Erlotinib	IC50 > 250 nM	176870	553	22037377
Ki11502	IC50 > 250 nM			22037377
Syk Inhibitor	IC50 > 250 nM	6419747	104279	22037377
Linifanib	Kd = 330 nM	11485656	223360	18183025
Afatinib	Kd = 340 nM	10184653	1173655	22037378
AST-487	Kd = 380 nM	11409972	574738	18183025
Doramapimod	Kd = 430 nM	156422	103667	15711537
Motesanib	Kd = 490 nM	11667893	572881	18183025
Dasatinib	IC50 = 500 nM	11153014	1421	22037377
Dovitinib	IC50 = 500 nM	57336746		22037377
MNK1 Inhibitor	IC50 = 500 nM	11644425	1240885	22037377
Nilotinib	IC50 = 500 nM	644241	255863	22037377
PKR Inhibitor	IC50 = 500 nM	6490494	235641	22037377
SU11652	IC50 = 500 nM	24906267	13485	22037377
Tozasertib	IC50 = 500 nM	5494449	572878	22037377
MLN8054	Kd = 580 nM	11712649	259084	18183025
Gefitinib	Kd = 590 nM	123631	939	18183025
Nintedanib	Kd = 940 nM	9809715	502835	22037378
Sunitinib	Kd = 960 nM	5329102	535	18183025
K-252a; Nocardiopsis sp.	IC50 > 1 µM	3813	281948	22037377
Lck Inhibitor	IC50 > 1 µM	6603792		22037377
p38 MAP Kinase Inhibitor	IC50 > 1 µM	4665	91730	22037377
PD169316	IC50 > 1 µM	4712	17331	22037377
PKCbII/EGFR Inhibitor	IC50 > 1 µM	6711154		22037377
SB218078	IC50 > 1 µM	447446	289422	22037377
Src Kinase Inhibitor I	IC50 > 1 µM	1474853	97771	22037377
SU6656	IC50 > 1 µM	5353978	605003	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Lestaurtinib	Kd = 1.2 µM	126565		22037378
SB203580	Kd = 1.2 µM	176155	10	18183025
SureCN5632345	Kd < 1.25 µM	44593646	515466	19035792
KW2449	Kd = 1.5 µM	11427553	1908397	22037378
RAF265	Kd = 1.5 µM	11656518	558752	18183025
SU14813	Kd = 2 µM	10138259	1721885	18183025
SB202190	Kd = 2.2 µM	5353940	278041	18183025
TG101348	Kd = 3.9 µM	16722836	1287853	22037378
BMS-690514	Kd < 4 µM	11349170		21531814
Pelitinib	Kd = 4.1 µM	6445562	607707	15711537

Disease Linkage

Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for EPHA6 in diverse human cancers of 438, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than 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: 0.14 % in 25741 diverse cancer specimens. This rate is 1.9-fold higher 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: 0.98 % in 913 skin cancers tested; 0.44 % in 1259 large intestine cancers tested; 0.4 % in 629 stomach cancers tested; 0.37 % in 1956 lung cancers tested; 0.29 % in 710 oesophagus cancers tested; 0.25 % in 152 biliary tract cancers tested; 0.21 % in 603 endometrium cancers tested; 0.16 % in 1512 liver cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R174C (9); R165C (3); R88C (3).

Comments:

Only 1 deletion, 2 insertions and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

EPHA6

OMIM Entry:

600066

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:

N-GlcNAcylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

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

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: