Nomenclature
Short Name:
EPHB4
Full Name:
Ephrin type-B receptor 4
Alias:
- EPB4
- Tyrosine-protein kinase receptor HTK
- EPH receptor B4
- HTK
- Mdk2
- MYK1
- Tyro11
Classification
Type:
Protein-tyrosine kinase
Group:
TK
Family:
Eph
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
108,270
# Amino Acids:
987
# mRNA Isoforms:
4
mRNA Isoforms:
108,270 Da (987 AA; P54760); 55,975 Da (516 AA; P54760-2); 45,195 Da (414 AA; P54760-4); 33,342 Da (306 AA; P54760-3)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
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Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K196.
N-GlcNAcylated:
N203, N335, N426.
Serine phosphorylated:
S332, S337, S575, S750, S757, S762, S769, S770, S776, S777, S872, S911, S943, S964.
Threonine phosphorylated:
T321, T322, T544, T587, T595, T713, T773, T775, T953, T976.
Tyrosine phosphorylated:
Y357, Y574, Y581, Y590, Y596, Y614, Y774, Y906, Y924, Y987.
Ubiquitinated:
K973.
Distribution
Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
56
814
29
895
14
198
15
135
15
212
18
483
67
971
99
2690
66
955
25
781
8
111
86
127
16
236
31
490
62
891
51
1434
30
441
17
342
10
145
73
109
13
183
37
326
52
747
179
657
10
139
40
405
9
131
12
108
15
212
30
532
9
130
15
86
51
732
127
4397
12
174
27
365
5
78
93
85
41
600
109
582
8
115
29
260
22
323
33
680
17
245
28
395
9
131
27
305
8
119
29
365
100
1447
67
2496
7
105
43
269
12
180
27
370
27
390
27
860
17
249
28
209
35
508
24
489
44
641
36
606
2
26
72
64
49
716
57
654
17
240
35
214
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
43.2
61
100
58.4
72.1
99
-
-
96
-
-
97
95.6
96.7
97
-
-
-
92.7
95.6
93
56.7
71.8
93
-
-
-
87.4
91.5
-
57.6
72.4
-
56
72.8
65
50.4
67.3
64
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | EFNB2 - P52799 |
| 2 | EGFR - P00533 |
Regulation
Activation:
Activated by binding ephrin-A1, B2, or B3.
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
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 #:
1
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 |
|---|
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Prostate cancer
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= +86, p<0.033); Brain glioblastomas (%CFC= -50, p<0.018); Breast epithelial carcinomas (%CFC= -52, p<0.014); Colon mucosal cell adenomas (%CFC= +91, p<0.0001); Ovary adenocarcinomas (%CFC= +129, p<0.011); and Uterine fibroids (%CFC= +51, p<0.053). The COSMIC website notes an up-regulated expression score for EPHB4 in diverse human cancers of 667, which is 1.4-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 22 for this protein kinase in human cancers was 0.4-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. EFNB2 binding to EphB4 can be inhibited with a L95R mutation.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25618 diverse cancer specimens. This rate is very similar (+ 10% 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: 0.35 % in 895 skin cancers tested; 0.34 % in 1270 large intestine cancers tested; 0.31 % in 629 stomach cancers tested; 0.19 % in 273 cervix cancers tested; 0.17 % in 603 endometrium cancers tested; 0.16 % in 710 oesophagus cancers tested; 0.16 % in 1956 lung cancers tested; 0.11 % in 548 urinary tract cancers tested; 0.09 % in 1512 liver cancers tested; 0.07 % in 1276 kidney cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,716 cancer specimens
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.