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Updated November 2019

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Nomenclature

Short Name:
BMX
Full Name:
Cytoplasmic tyrosine-protein kinase BMX
Alias:
  • BMX NON-receptor tyrosine kinase
  • Bone marrow kinase BMX
  • Kinase Etk
  • NTK38
  • Protein tyrosine kinase BMX
  • PSCTK3
  • Cytoplasmic BMX
  • EC 2.7.10.2
  • Epithelial and endothelial tyrosine kinase
  • ETK

Classification

Type:
Protein-tyrosine kinase
Group:
TK
Family:
Tec
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 660
Entrez-Protein Entry: NP_001712
GeneCards Entry: ETK
KinBASE Entry: BMX
OMIM Entry: 300101
Pfam Entry: P51813
PhosphoNET Entry: P51813
Phosphosite Plus Entry: 843
Protein Data Bank Entry: 2EKX
ScanSite Entry: P51813
Source Entry: BMX
UCSD-Nature Entry: A000384
UniProt Entry: P51813
Kinexus Products: BMX
Bone marrow X protein-tyrosine kinase Y40 phosphosite-specific antibody AB-PK545
Bone marrow X protein-tyrosine kinase (N37-Y43, human) pY40 phosphopeptide - Powder PE-04AIT95

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
78,011
# Amino Acids:
675
# mRNA Isoforms:
1
mRNA Isoforms:
78,011 Da (675 AA; P51813)
4D Structure:
Interacts with RUFY1 and RUFY2.
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
3SXR

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
4 111 PH
113 149 BTK
296 392 SH2
417 666 TyrKc
417 668 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Bone marrow X protein-tyrosine kinase Y40 phosphosite-specific antibody AB-PK545
○ Bone marrow X protein-tyrosine kinase (N37-Y43, human) pY40 phosphopeptide - Powder PE-04AIT95
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K172, K181, K337, K343, K347, K395.
Serine phosphorylated:

S186, S226, S260, S261, S324, S425, S568.
Tyrosine phosphorylated:

Y40+, Y216, Y330, Y365, Y440, Y566+.
Ubiquitinated:
K413.
 

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:
  • adipose
    37

    816

    16

    1053

  • adrenal
    0.6

    13

    9

    14

  • bladder
    4

    98

    19

    206

  • brain
    24

    526

    62

    1578

  • breast
    12

    272

    14

    281

  • cervix
    0.5

    12

    37

    12

  • colon
    12

    260

    19

    484

  • heart
    25

    548

    38

    1345

  • intestine
    9

    210

    10

    205

  • kidney
    2

    42

    44

    59

  • liver
    1.2

    26

    32

    57

  • lung
    22

    484

    102

    587

  • lymphnode
    3

    57

    30

    78

  • ovary
    0.5

    12

    8

    5

  • pancreas
    3

    71

    28

    156

  • pituitary
    0.4

    9

    7

    8

  • prostate
    1.1

    24

    114

    48

  • salivarygland
    2

    55

    24

    116

  • skeletalmuscle"
    1.2

    26

    61

    54

  • skin
    13

    297

    56

    346

  • spinalcord
    3

    66

    27

    147

  • spleen
    2

    37

    30

    70

  • stomach
    2

    44

    28

    59

  • testis
    2

    36

    25

    82

  • thymus
    3

    58

    27

    158

  • thyroid
    39

    877

    45

    2015

  • tonsil
    0.8

    17

    33

    27

  • trachea
    2

    54

    26

    90

  • uterus
    3

    57

    26

    76

  • reticulocytes"
    1.5

    33

    14

    39

  • t-lymphocytes
    22

    489

    30

    244

  • b-lymphocytes
    100

    2235

    21

    4186

  • neutrophils
    6

    129

    55

    359

  • macrophages
    24

    541

    31

    564

  • sperm
    2

    47

    31

    74

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    49.8

    68

    93
  • tableheader
    96.8

    97.8

    97.5
  • tableheader
    -

    -

    93
  • tableheader
    -

    -

    -
  • tableheader
    68.3

    71.4

    92
  • tableheader
    -

    -

    -
  • tableheader
    87.8

    92.4

    91
  • tableheader
    28.4

    45.3

    90
  • tableheader
    -

    -

    -
  • tableheader
    65.6

    73.6

    -
  • tableheader
    49.2

    68.3

    68
  • tableheader
    28.1

    46.8

    -
  • tableheader
    46.4

    65.8

    -
  • tableheader
    -

    -

    -
  • tableheader
    35.5

    52.2

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 PAK1 - Q13153
2 CASP3 - P42574
3 STAT3 - P40763
4 GAB1 - Q13480
5 TP53 - P04637
6 BTK - Q06187
7 ITK - Q08881
8 CRK - P46108
9 ERBB2 - P04626
10 EGFR - P00533
11 BLNK - Q8WV28
 

Regulation

Activation:
Phosphorylation of Tyr-40 increases phosphotransferase activity and induced interaction with FAK. Phosphorylation of Tyr-566 induces interaction with PIK3R1 and STAT3. It is likely that activation also occurs through binding of phosphoinositides to the PH domain.
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

Kinections Map

Click here to download a PPT of the image below
 
Kinections GIF
 

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
TEC P42680 Y216 SSTSLAQYDSNSKKI
ITK Q08881 Y216 SSTSLAQYDSNSKKI
BTK Q06187 Y216 SSTSLAQYDSNSKKI
SRC P12931 Y566 RYVLDDQYVSSVGTK +
 

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
Pim1 P11309 Y309 EWIRYHRYHGRSAAV +
RUFY1 Q96T51 Y389 TKVELETYKQTRQGL
RUFY1 Q96T51 Y400 RQGLDEMYSDVWKQL
 

Protein Kinase Specificity

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

Kinections GIF
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
2hiw IC50 = 1.4 nM 10062694 18077425
Dasatinib Kd = 1.4 nM 11153014 1421 18183025
Bosutinib IC50 = 7.9 nM 5328940 288441 19039322
WZ3146 Kd < 20 nM 44607360 20033049
HDS029 IC50 < 25 nM 11566580 203644 22037377
CHEMBL249097 Kd = 36 nM 25138012 249097 19035792
Ponatinib IC50 = 47.1 nM 24826799 20513156
Gö6976 IC50 > 50 nM 3501 302449 22037377
K-252a; Nocardiopsis sp. IC50 > 50 nM 3813 281948 22037377
Lck Inhibitor IC50 > 50 nM 6603792 22037377
Canertinib IC50 = 62 nM 156414 31965 18667312
AT9283 IC50 > 100 nM 24905142 19143567
MK5108 IC50 = 100 nM 24748204 20053775
GSK-3 Inhibitor IX IC50 > 150 nM 5287844 409450 22037377
PP1 Analog II; 1NM-PP1 IC50 > 150 nM 5154691 573578 22037377
SB218078 IC50 > 150 nM 447446 289422 22037377
TWS119 IC50 > 150 nM 9549289 405759 22037377
Staurosporine Kd = 170 nM 5279 18183025
Foretinib Kd = 200 nM 42642645 1230609 22037378
Lestaurtinib Kd = 200 nM 126565 22037378
GSK-3 Inhibitor XIII IC50 > 250 nM 6419766 359482 22037377
IDR E804 IC50 > 250 nM 6419764 1802727 22037377
Ki11502 IC50 > 250 nM 22037377
N-Benzoylstaurosporine IC50 > 250 nM 56603681 608533 22037377
NU6140 IC50 > 250 nM 10202471 1802728 22037377
PP121 IC50 < 250 nM 24905142 18849971
Tozasertib IC50 > 250 nM 5494449 572878 22037377
PD168393 IC50 = 303 nM 4708 285063 18667312
AMG458 IC50 = 363 nM 16086104 386661 18553959
CHEMBL383899 IC50 = 386 nM 9549303 383899 18077363
TG101209 IC50 = 500 nM 16722832 17541402
BMS-690514 Kd < 600 nM 11349170 21531814
Alisertib IC50 < 700 nM 24771867 22016509
JNJ-28312141 Kd = 780 nM 22037378
CHEMBL215803 IC50 > 1 µM 16046126 215803 16876403
CHEMBL566515 Kd = 1 µM 44478401 566515 19788238
CP673451 IC50 > 1 µM 10158940 15705896
GSK-3 Inhibitor X IC50 > 1 µM 6538818 430226 22037377
Icotinib IC50 > 1 µM 22024915 22112293
IKK-2 Inhibitor IV IC50 > 1 µM 9903786 257167 22037377
Silmitasertib IC50 > 1 µM 24748573 21174434
SNS314 IC50 > 1 µM 16047143 514582 18678489
SureCN10063060 Ki > 1 µM 52936621 21391610
WZ4002 Kd > 1 µM 44607530 20033049
NVP-TAE684 Kd = 1.1 µM 16038120 509032 22037378
TG101348 Kd = 1.2 µM 16722836 1287853 22037378
Hesperadin Kd < 1.25 µM 10142586 514409 19035792
SureCN7018367 Kd < 1.25 µM 18792927 450519 19035792
CHEMBL1240703 Kd = 1.7 µM 52945601 1240703 19654408
KW2449 Kd = 1.9 µM 11427553 1908397 22037378
MLN8054 Kd = 3.1 µM 11712649 259084 18183025
SureCN4875304 IC50 > 3.5 µM 46871765 20472445
Crizotinib Kd = 3.6 µM 11626560 601719 22037378
JNJ-28871063 IC50 > 4 µM 17747413 17975007
JNJ-7706621 Kd = 4.7 µM 5330790 191003 18183025
 

Disease Linkage

General Disease Association:

Cancer
Specific Cancer Types:
Prostate cancer
Comments:
BMX has been demonstrated to prevent apoptosis of nasopharyngeal carcinomas.
 
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: Bladder carcinomas (%CFC= -45, p<0.0002); Brain oligodendrogliomas (%CFC= +62, p<0.102); Skin melanomas - malignant (%CFC= -72, p<0.001); and Vulvar intraepithelial neoplasia (%CFC= -56, p<0.025). The COSMIC website notes an up-regulated expression score for BMX in diverse human cancers of 453, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 144 for this protein kinase in human cancers was 2.4-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 25033 diverse cancer specimens. This rate is very similar (+ 3% 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: 0.37 % in 602 endometrium cancers tested; 0.35 % in 805 skin cancers tested; 0.35 % in 1093 large intestine cancers tested; 0.14 % in 1807 lung cancers tested.
Frequency of Mutated Sites:

None > 7 in 20,285 cancer specimens; 6 were S212S silent mutations
Comments:
Only 1 insertion, and no deletions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
BMX
OMIM Entry:
300101
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