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Updated November 2019

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Nomenclature

Short Name:
TAO3
Full Name:
Serine-threonine-protein kinase TAO3
Alias:
  • DPK
  • EC 2.7.11.1
  • TAOK3
  • JIK
  • Kinase TAO3
  • MAP3K18
  • TAO kinase 3

Classification

Type:
Protein-serine/threonine kinase
Group:
STE
Family:
STE20
SubFamily:
TAO
 
 

Specific Links

Entrez-Gene Entry: 51347
Entrez-Protein Entry: NP_057365
KinBASE Entry: TAO3
Pfam Entry: Q9H2K8
PhosphoNET Entry: Q9H2K8
Phosphosite Plus Entry: 2524
UCSD-Nature Entry: A000042
UniProt Entry: Q9H2K8
Kinexus Products: TAO3
Serine/threonine-protein kinase TAO3 pan-specific antibody AB-NK087-2
Serine/threonine-protein kinase TAO3 (S331-S349, human) peptide - Powder PE-01BFJ90T

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):
105,406
# Amino Acids:
898
# mRNA Isoforms:
1
mRNA Isoforms:
105,406 Da (898 AA; Q9H2K8)
4D Structure:
Self-associates.
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
24 277 Pkinase
454 499 Coiled-coil
549 569 Coiled-coil
575 595 Coiled-coil
621 643 Coiled-coil
758 778 Coiled-coil
795 834 Coiled-coil
839 878 Coiled-coil
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Serine/threonine-protein kinase TAO3 pan-specific antibody AB-NK087-2
○ Serine/threonine-protein kinase TAO3 (S331-S349, human) peptide - Powder PE-01BFJ90T
 

Post-translation Modifications

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

S173+, S177+, S324+, S331, S336, S354, S359, S442, S551, S782.
Threonine phosphorylated:

T181+, T316, T335, T357, T437, T573, T745.
Tyrosine phosphorylated:

Y103, Y305, Y429, Y897.
 

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
    44

    860

    29

    919

  • adrenal
    3

    56

    16

    41

  • bladder
    16

    318

    22

    331

  • brain
    29

    563

    113

    837

  • breast
    49

    945

    25

    683

  • cervix
    3

    63

    74

    45

  • colon
    24

    464

    35

    508

  • heart
    66

    1292

    59

    3081

  • intestine
    36

    702

    17

    625

  • kidney
    7

    142

    108

    170

  • liver
    8

    152

    47

    174

  • lung
    30

    577

    200

    601

  • lymphnode
    14

    267

    44

    364

  • ovary
    4

    78

    15

    71

  • pancreas
    10

    186

    40

    268

  • pituitary
    6

    107

    16

    90

  • prostate
    7

    134

    219

    241

  • salivarygland
    11

    216

    31

    214

  • skeletalmuscle"
    5

    103

    103

    115

  • skin
    34

    659

    109

    679

  • spinalcord
    14

    273

    41

    375

  • spleen
    11

    213

    45

    257

  • stomach
    18

    342

    24

    321

  • testis
    7

    134

    33

    149

  • thymus
    12

    224

    41

    275

  • thyroid
    39

    749

    72

    1099

  • tonsil
    11

    217

    47

    251

  • trachea
    7

    133

    33

    152

  • uterus
    12

    231

    33

    285

  • reticulocytes"
    3

    51

    28

    40

  • t-lymphocytes
    19

    367

    24

    227

  • b-lymphocytes
    100

    1943

    36

    4002

  • neutrophils
    5

    95

    74

    164

  • macrophages
    51

    983

    52

    656

  • sperm
    7

    141

    35

    125

 

Evolution

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

    100

    100
  • tableheader
    92.3

    92.4

    94
  • tableheader
    25.3

    37

    -
  • tableheader
    -

    -

    98
  • tableheader
    -

    -

    76
  • tableheader
    98.3

    99.2

    98
  • tableheader
    -

    -

    -
  • tableheader
    95.5

    97.7

    95.5
  • tableheader
    95.3

    97.9

    95
  • tableheader
    -

    -

    -
  • tableheader
    66.3

    77.8

    -
  • tableheader
    94

    97.7

    94
  • tableheader
    89.4

    95.2

    64
  • tableheader
    24.9

    37.9

    84.5
  • tableheader
    -

    -

    -
  • tableheader
    25.1

    41.6

    -
  • tableheader
    -

    -

    -
  • tableheader
    38

    57

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • 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
Staurosporine Kd = 220 pM 5279 22037378
AST-487 Kd = 5.8 nM 11409972 574738 22037378
PHA-665752 Kd = 43 nM 10461815 450786 22037378
NVP-TAE684 Kd = 44 nM 16038120 509032 22037378
Pazopanib Kd = 45 nM 10113978 477772 22037378
Aurora A Inhibitor 1 (DF) Kd < 50 nM 21992004
Cdk1/2 Inhibitor III IC50 > 50 nM 5330812 261720 22037377
AT7519 Kd = 57 nM 11338033 22037378
Tozasertib Kd = 81 nM 5494449 572878 22037378
Lestaurtinib Kd = 86 nM 126565 22037378
Ruboxistaurin Kd = 97 nM 153999 91829 22037378
Alvocidib Kd = 99 nM 9910986 428690 22037378
JAK3 Inhibitor VI IC50 > 150 nM 16760524 22037377
K-252a; Nocardiopsis sp. IC50 > 150 nM 3813 281948 22037377
PKR Inhibitor IC50 > 150 nM 6490494 235641 22037377
SB218078 IC50 > 150 nM 447446 289422 22037377
Aurora A Inhibitor 23 (DF) Kd < 200 nM 21992004
R547 Kd = 210 nM 6918852 22037378
Sunitinib Kd = 210 nM 5329102 535 19654408
JNJ-7706621 IC50 > 250 nM 5330790 191003 22037377
N-Benzoylstaurosporine IC50 > 250 nM 56603681 608533 22037377
SU9516 IC50 > 250 nM 5289419 258805 22037377
Linifanib Kd = 260 nM 11485656 223360 22037378
SU14813 Kd = 310 nM 10138259 1721885 22037378
Bosutinib Kd = 340 nM 5328940 288441 22037378
Crizotinib Kd = 490 nM 11626560 601719 22037378
PP242 Kd = 490 nM 25243800 22037378
BCP9000906 IC50 = 500 nM 5494425 21156 22037377
IDR E804 IC50 = 500 nM 6419764 1802727 22037377
PKR Inhibitor; Negative Control IC50 = 500 nM 16760619 22037377
SU11652 IC50 = 500 nM 24906267 13485 22037377
SU6656 IC50 = 500 nM 5353978 605003 22037377
Ruxolitinib Kd = 590 nM 25126798 1789941 22037378
AC1NS7CD Kd = 620 nM 5329665 295136 22037378
SNS032 Kd = 620 nM 3025986 296468 22037378
RAF265 Kd = 720 nM 11656518 558752 22037378
AG-E-60384 IC50 > 1 µM 6419741 413188 22037377
Alsterpaullone; 2-Cyanoethyl IC50 > 1 µM 16760286 260138 22037377
Bisindolylmaleimide I IC50 > 1 µM 2396 7463 22037377
Flt-3 Inhibitor II IC50 > 1 µM 11601743 377193 22037377
GSK-3 Inhibitor IX IC50 > 1 µM 5287844 409450 22037377
Indirubin-3′-monoxime IC50 > 1 µM 5326739 22037377
KW2449 Kd = 1 µM 11427553 1908397 22037378
SU11274 IC50 > 1 µM 9549297 261641 22037377
Syk Inhibitor IC50 > 1 µM 6419747 104279 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
A674563 Kd = 1.1 µM 11314340 379218 22037378
GSK1838705A Kd = 1.4 µM 25182616 464552 22037378
BI2536 Kd = 1.7 µM 11364421 513909 22037378
Nilotinib Kd = 1.7 µM 644241 255863 22037378
TG101348 Kd = 1.9 µM 16722836 1287853 22037378
BMS-690514 Kd < 2 µM 11349170 21531814
JNJ-28312141 Kd = 2.2 µM 22037378
Dasatinib Kd = 2.3 µM 11153014 1421 22037378
TG100115 Kd = 2.4 µM 10427712 230011 22037378
Sorafenib Kd = 2.7 µM 216239 1336 19654408
Neratinib Kd = 4.2 µM 9915743 180022 22037378
R406 Kd = 4.6 µM 11984591 22037378
 

Disease Linkage

Comments:
TAO3 was found to link with morphine requirement and postoperative pain in a retrospective pediatric day surgery population.
 
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= +65, p<0.0004); Brain oligodendrogliomas (%CFC= -83, p<0.084); Uterine fibroids (%CFC= +72, p<0.001); and Uterine leiomyomas from fibroids (%CFC= +102, p<0.001). The COSMIC website notes an up-regulated expression score for TAO3 in diverse human cancers of 342, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 111 for this protein kinase in human cancers was 1.9-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.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 24900 diverse cancer specimens. This rate is only -23 % 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: 0.29 % in 575 stomach cancers tested; 0.26 % in 1270 large intestine cancers tested; 0.16 % in 273 cervix cancers tested; 0.14 % in 1634 lung cancers tested; 0.13 % in 864 skin cancers tested; 0.11 % in 710 oesophagus cancers tested; 0.11 % in 603 endometrium cancers tested; 0.09 % in 127 biliary tract cancers tested; 0.08 % in 548 urinary tract cancers tested; 0.07 % in 1512 liver cancers tested; 0.05 % in 238 bone cancers tested; 0.04 % in 2082 central nervous system cancers tested; 0.04 % in 1316 breast cancers tested; 0.03 % in 833 ovary cancers tested; 0.03 % in 1276 kidney cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: P20T (3).
Comments:
Only 2 insertions and no insertions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
TAOK3
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