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Updated November 2019

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Nomenclature

Short Name:
TSSK1
Full Name:
Testis-specific serine-threonine protein kinase 1
Alias:
  • EC 2.7.11.1
  • FKSG81
  • ST2A
  • STK22A
  • STK22D
  • TSSK7P; Testis-specific kinase 1; Testis-specific serine kinase 1; TSK-1; TSSK-1;
  • Serine/threonine protein kinase 22A
  • Serine/threonine protein kinase FKSG81
  • SPOGA1
  • SPOGA4

Classification

Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
TSSK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 83942
Entrez-Protein Entry: NP_114417
Pfam Entry: Q9BXA7
PhosphoNET Entry: Q9BXA7
Phosphosite Plus Entry: 787
UCSD-Nature Entry: A003173
UniProt Entry: Q9BXA7

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):
41,618
# Amino Acids:
367
# mRNA Isoforms:
1
mRNA Isoforms:
41,618 Da (367 AA; Q9BXA7)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
12 272 Pkinase
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K159.
Serine phosphorylated:

S172+, S279, S281, S290, S291.
Tyrosine phosphorylated:

Y197, Y207, Y216.
 

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
    5

    282

    16

    582

  • adrenal
    1.3

    75

    10

    151

  • bladder
    0

    2

    1

    0

  • brain
    3

    191

    40

    358

  • breast
    5

    270

    11

    214

  • cervix
    0

    1

    37

    1

  • colon
    0

    2

    15

    1

  • heart
    8

    450

    15

    518

  • intestine
    3

    198

    10

    206

  • kidney
    0.6

    33

    33

    117

  • liver
    0.9

    51

    12

    112

  • lung
    9

    515

    74

    492

  • lymphnode
    0.4

    23

    14

    54

  • ovary
    1.1

    63

    8

    132

  • pancreas
    1.2

    68

    9

    164

  • pituitary
    0.7

    43

    9

    82

  • prostate
    0.4

    21

    15

    51

  • salivarygland
    0.7

    43

    8

    79

  • skeletalmuscle"
    2

    90

    39

    397

  • skin
    4

    215

    58

    260

  • spinalcord
    1

    57

    8

    104

  • spleen
    0

    2

    8

    1

  • stomach
    0.1

    4

    2

    1

  • testis
    3

    158

    10

    148

  • thymus
    0.7

    44

    8

    76

  • thyroid
    6

    372

    24

    426

  • tonsil
    0.4

    21

    17

    52

  • trachea
    0.7

    43

    8

    74

  • uterus
    1

    57

    8

    99

  • reticulocytes"
    0.8

    47

    14

    22

  • t-lymphocytes
    8

    449

    18

    331

  • b-lymphocytes
    18

    1071

    29

    2476

  • neutrophils
    0

    2

    17

    1

  • macrophages
    11

    675

    26

    589

  • sperm
    100

    5903

    20

    10438

 

Evolution

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

    100

    100
  • tableheader
    97.5

    98.1

    97.5
  • tableheader
    65.7

    77.7

    96
  • tableheader
    -

    -

    86
  • tableheader
    -

    -

    -
  • tableheader
    82.1

    87.8

    84
  • tableheader
    -

    -

    -
  • tableheader
    83.7

    89.7

    85
  • tableheader
    21

    32.5

    86
  • tableheader
    -

    -

    -
  • tableheader
    66.5

    79

    -
  • tableheader
    21.6

    32.1

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    48
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    42
  • tableheader
    41.7

    57.2

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    30.3

    43.4

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
Activated by phosphorylation on Thr-174, potentially by autophosphorylation.
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
TTT-3002 IC50 < 4 nM
Staurosporine Kd = 24 nM 5279 18183025
K-252a; Nocardiopsis sp. IC50 < 25 nM 3813 281948 22037377
NVP-TAE684 Kd = 25 nM 16038120 509032 22037378
Cdk1/2 Inhibitor III IC50 > 50 nM 5330812 261720 22037377
Gö6976 IC50 > 50 nM 3501 302449 22037377
N-Benzoylstaurosporine IC50 > 50 nM 56603681 608533 22037377
SU11652 IC50 > 50 nM 24906267 13485 22037377
Amgen TBK 1 inhibitor (Compound II) IC50 < 80 nM
Lestaurtinib Kd = 98 nM 126565 22037378
AT9283 IC50 > 100 nM 24905142 19143567
NU6140 IC50 > 150 nM 10202471 1802728 22037377
SB218078 IC50 > 150 nM 447446 289422 22037377
SU11274 IC50 > 150 nM 9549297 261641 22037377
Sunitinib IC50 > 150 nM 5329102 535 22037377
Syk Inhibitor IC50 > 150 nM 6419747 104279 22037377
BCP9000906 IC50 > 250 nM 5494425 21156 22037377
JAK3 Inhibitor VI IC50 > 250 nM 16760524 22037377
Syk Inhibitor II IC50 > 250 nM 16760670 22037377
VEGFR2 Kinase Inhibitor II IC50 > 250 nM 5329155 88606 22037377
GSK1838705A Kd = 470 nM 25182616 464552 22037378
Dovitinib IC50 = 500 nM 57336746 22037377
Momelotinib IC50 < 750 nM 25062766 19295546
CZC-25146 IC50 < 800 nM
A 443654 IC50 < 1 µM 10172943 379300 19465931
Aloisine A IC50 > 1 µM 5326843 75680 22037377
Aloisine; RP106 IC50 > 1 µM 44350092 126343 22037377
Alsterpaullone; 2-Cyanoethyl IC50 > 1 µM 16760286 260138 22037377
GSK461364A IC50 = 1 µM 15983966 1908394
HG-10-102-01 IC50 = 1 µM
IKK-2 Inhibitor IV IC50 > 1 µM 9903786 257167 22037377
MK5108 IC50 > 1 µM 24748204 20053775
Novartis 12a (PKD1) IC50 = 1 µM
PD158780 IC50 > 1 µM 4707 53753 22037377
PDGF Receptor Tyrosine Kinase Inhibitor III IC50 > 1 µM 10907042 22037377
PKR Inhibitor IC50 > 1 µM 6490494 235641 22037377
Silmitasertib IC50 > 1 µM 24748573 21174434
SNS314 IC50 > 1 µM 16047143 514582 18678489
SU6656 IC50 = 1 µM 5353978 605003
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
TG101348 Kd = 1.3 µM 16722836 1287853 22037378
CHEMBL248757 Ki > 1.596 µM 44444843 248757 17935989
PHA-665752 Kd = 2.1 µM 10461815 450786 22037378
KW2449 Kd = 2.3 µM 11427553 1908397 22037378
HG-9-91-01 IC50 > 3 µM
JNJ-28312141 Kd = 3.2 µM 22037378
JNJ-28871063 IC50 > 4 µM 17747413 17975007
SureCN2579964 IC50 < 4 µM 290221 233000 22934575
BI2536 IC50 > 4.5 µM 11364421 513909
Bosutinib Kd = 4.6 µM 5328940 288441 22037378
 

Disease Linkage

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. A T174A mutation in TSSK1 can lead to abrogated phosphotransferase activity, while a T174E mutation can yield a constitutively active protein kinase.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.13 % in 24447 diverse cancer specimens. This rate is 1.8-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: 1.09 % in 1229 large intestine cancers tested; 0.76 % in 864 skin cancers tested; 0.45 % in 603 endometrium cancers tested; 0.29 % in 569 stomach cancers tested; 0.2 % in 548 urinary tract cancers tested; 0.15 % in 1608 lung cancers tested; 0.11 % in 238 bone cancers tested; 0.11 % in 1289 breast cancers tested; 0.1 % in 273 cervix cancers tested; 0.08 % in 710 oesophagus cancers tested; 0.07 % in 1982 haematopoietic and lymphoid cancers tested; 0.04 % in 1437 pancreas cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R9* (4), E301K (4); R237C (3); R168* (3).
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
TSSK1B
OMIM Entry:
610709
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