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Updated November 2019

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Nomenclature

Short Name:
BIKE
Full Name:
BMP-2 inducible protein kinase
Alias:
  • BM2K
  • BMP2K
  • Kinase BIKE
  • BMP2 inducible kinase
  • DKFZp434K0614
  • EC 2.7.11.1
  • HRIHFB2017

Classification

Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NAK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 55589
Entrez-Protein Entry: NP_942595
KinBASE Entry: BIKE
Pfam Entry: Q9NSY1
PhosphoNET Entry: Q9NSY1
Phosphosite Plus Entry: 2191
UCSD-Nature Entry: A003150
UniProt Entry: Q9NSY1

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):
129,172
# Amino Acids:
1161
# mRNA Isoforms:
3
mRNA Isoforms:
129,172 Da (1161 AA; Q9NSY1); 75,812 Da (677 AA; Q9NSY1-3); 73,838 Da (662 AA; Q9NSY1-2)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
5I3O

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
51 316 Pkinase
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:

S14, S378, S665, S689, S715, S728, S740, S742, S791, S817, S818, S824, S826, S843, S947, S949, S974, S979, S980, S1029, S1031, S1032, S1039, S1041, S1076, S1080, S1089, S1107, S1111, S1114.
Threonine phosphorylated:

T383, T394, T829, T834, T935, T1002, T1011, T1014, T1037, T1097.
Tyrosine phosphorylated:

Y257, Y594, Y813, Y820, Y1012.
Ubiquitinated:
K991.
 

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
    93

    1001

    70

    1204

  • adrenal
    2

    19

    27

    16

  • bladder
    17

    185

    18

    253

  • brain
    23

    249

    229

    535

  • breast
    70

    761

    65

    619

  • cervix
    2

    21

    169

    30

  • colon
    11

    123

    75

    328

  • heart
    100

    1082

    77

    2925

  • intestine
    43

    460

    31

    340

  • kidney
    4

    39

    183

    55

  • liver
    7

    72

    55

    117

  • lung
    52

    565

    312

    499

  • lymphnode
    16

    168

    62

    386

  • ovary
    2

    17

    18

    9

  • pancreas
    6

    67

    43

    101

  • pituitary
    2

    22

    39

    19

  • prostate
    17

    189

    374

    1688

  • salivarygland
    8

    87

    31

    152

  • skeletalmuscle"
    2

    27

    195

    49

  • skin
    50

    544

    271

    550

  • spinalcord
    24

    262

    39

    469

  • spleen
    22

    235

    46

    463

  • stomach
    13

    145

    22

    200

  • testis
    43

    466

    31

    885

  • thymus
    11

    121

    39

    202

  • thyroid
    57

    613

    143

    817

  • tonsil
    14

    148

    65

    351

  • trachea
    8

    91

    31

    147

  • uterus
    11

    116

    31

    189

  • reticulocytes"
    11

    124

    84

    143

  • t-lymphocytes
    37

    400

    48

    396

  • b-lymphocytes
    47

    508

    76

    543

  • neutrophils
    12

    130

    193

    514

  • macrophages
    79

    852

    156

    705

  • sperm
    8

    84

    96

    98

 

Evolution

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

    100

    100
  • tableheader
    80.9

    80.9

    100
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    87
  • tableheader
    -

    -

    68
  • tableheader
    88.5

    91.2

    90
  • tableheader
    -

    -

    -
  • tableheader
    83.2

    88.2

    83
  • tableheader
    38.5

    50

    82
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    72.5

    80.8

    88
  • tableheader
    -

    -

    68
  • tableheader
    37.9

    45.6

    72
  • tableheader
    -

    -

    -
  • tableheader
    26.9

    41.7

    -
  • tableheader
    28.9

    38.4

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    21.4

    38.2

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

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
Nintedanib Kd = 2.2 nM 9809715 502835 22037378
Staurosporine Kd = 3.7 nM 5279 15711537
Sunitinib Kd = 5.5 nM 5329102 535 18183025
KW2449 Kd = 9.6 nM 11427553 1908397 22037378
Hesperadin Kd < 10 nM 10142586 514409 19035792
Lestaurtinib Kd = 16 nM 126565 22037378
1;9-Pyrazoloanthrone Kd = 25 nM 8515 7064 15711537
SU14813 Kd = 27 nM 10138259 1721885 18183025
TG101348 Kd = 32 nM 16722836 1287853 22037378
PHA-665752 Kd = 47 nM 10461815 450786 22037378
Dovitinib Kd = 54 nM 57336746 18183025
Tozasertib Kd = 65 nM 5494449 572878 18183025
A674563 Kd = 120 nM 11314340 379218 22037378
AC1NS4N8 Kd < 150 nM 5353854 101797 19035792
IKK-2 Inhibitor IV Kd < 150 nM 9903786 257167 19035792
JNJ-7706621 Kd = 180 nM 5330790 191003 18183025
Ruxolitinib Kd = 210 nM 25126798 1789941 22037378
N-Benzoylstaurosporine Kd = 220 nM 56603681 608533 18183025
Bosutinib Kd = 350 nM 5328940 288441 22037378
Ruboxistaurin Kd = 430 nM 153999 91829 18183025
GSK461364A Kd = 470 nM 15983966 1908394 22037378
Pelitinib Kd = 540 nM 6445562 607707 15711537
Aurora A Inhibitor 23 (DF) Kd < 600 nM 21992004
Crizotinib Kd = 740 nM 11626560 601719 22037378
Aurora A Inhibitor 1 (DF) Kd < 800 nM 21992004
Axitinib Kd = 1 µM 6450551 1289926 22037378
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Erlotinib Kd = 1.2 µM 176870 553 18183025
LKB1(AAK1 dual inhibitor) Kd < 1.25 µM 44588117 516312 19035792
SureCN373973 Kd < 1.25 µM 9818573 30678 19035792
Canertinib Kd = 1.6 µM 156414 31965 15711537
NVP-TAE684 Kd = 1.9 µM 16038120 509032 22037378
R406 Kd = 1.9 µM 11984591 22037378
CHEMBL1240703 Kd = 2.1 µM 52945601 1240703 19654408
AC1O6ZUA Kd < 2.5 µM 6539569 408019 19035792
Enzastaurin Kd = 2.9 µM 176167 300138 22037378
 

Disease Linkage

Comments:
BIKE may be a tumour requiring protein (TRP), since it displays extremely low rates of mutation in human cancers.
 
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: Brain glioblastomas (%CFC= -85, p<0.043); Brain oligodendrogliomas (%CFC= -72, p<0.088); Breast epithelial cell carcinomas (%CFC= +56, p<0.021); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +135, p<0.006); Clear cell renal cell carcinomas (cRCC) (%CFC= +77, p<0.101); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +446, p<0.029); and Ovary adenocarcinomas (%CFC= +49, p<0.03). The COSMIC website notes an up-regulated expression score for BIKE in diverse human cancers of 341, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 5 for this protein kinase in human cancers was 0.1-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: 0.02 % in 24832 diverse cancer specimens. This rate is -80 % lower than the average rate of 0.075 % calculated for human protein kinases in general. Such a very low frequency of mutation in human cancers is consistent with this protein kinase playing a role as a tumour requiring protein (TRP).
Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.03 % in 603 endometrium cancers tested; 0.02 % in 864 skin cancers tested; 0.02 % in 1512 liver cancers tested.
Frequency of Mutated Sites:

None > 6 in 20,059 cancer specimens
Comments:
No deletions, insertions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
BMP2K
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