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Updated November 2019

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Nomenclature

Short Name:
MSSK1
Full Name:
Serine-threonine-protein kinase 23
Alias:
  • EC 2.7.11.1
  • Kinase MSSK1
  • SRPK3
  • STK23
  • MGC102944
  • MSSK-1
  • Muscle-specific serine kinase 1
  • Serine/threonine protein kinase 23

Classification

Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
SRPK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 26576
Entrez-Protein Entry: NP_055185
KinBASE Entry: MSSK1
Pfam Entry: Q9UPE1
PhosphoNET Entry: Q9UPE1
Phosphosite Plus Entry: 767
UCSD-Nature Entry: A003019
UniProt Entry: Q9UPE1

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):
58,997
# Amino Acids:
533
# mRNA Isoforms:
4
mRNA Isoforms:
62,014 Da (567 AA; Q9UPE1); 61,886 Da (566 AA; Q9UPE1-4); 58,997 Da (533 AA; Q9UPE1-3); 55,327 Da (491 AA; Q9UPE1-2)
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
79 531 Pkinase
 

Post-translation Modifications

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

S2, S4, S330.
Threonine phosphorylated:

T5, T426.
 

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
    100

    1295

    16

    2142

  • adrenal
    5

    66

    10

    56

  • bladder
    41

    536

    15

    968

  • brain
    53

    682

    60

    1454

  • breast
    33

    424

    14

    411

  • cervix
    2

    21

    37

    24

  • colon
    28

    360

    19

    679

  • heart
    69

    894

    35

    1115

  • intestine
    17

    222

    10

    191

  • kidney
    18

    232

    58

    567

  • liver
    25

    326

    28

    732

  • lung
    49

    632

    109

    658

  • lymphnode
    32

    411

    26

    1195

  • ovary
    4

    47

    9

    42

  • pancreas
    37

    484

    25

    1203

  • pituitary
    5

    70

    8

    36

  • prostate
    12

    149

    112

    377

  • salivarygland
    25

    323

    22

    574

  • skeletalmuscle"
    61

    788

    71

    496

  • skin
    23

    292

    56

    324

  • spinalcord
    28

    362

    24

    856

  • spleen
    26

    339

    26

    1055

  • stomach
    50

    650

    16

    1681

  • testis
    19

    242

    22

    407

  • thymus
    33

    427

    24

    1125

  • thyroid
    32

    419

    42

    582

  • tonsil
    19

    247

    29

    755

  • trachea
    57

    735

    22

    2434

  • uterus
    30

    388

    22

    890

  • reticulocytes"
    6

    84

    14

    23

  • t-lymphocytes
    21

    275

    18

    178

  • b-lymphocytes
    63

    813

    21

    934

  • neutrophils
    10

    130

    49

    274

  • macrophages
    68

    886

    26

    763

  • sperm
    4

    46

    22

    47

 

Evolution

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

    100

    100
  • tableheader
    70.2

    81.6

    97
  • tableheader
    68.3

    80.3

    98
  • tableheader
    -

    -

    96
  • tableheader
    -

    -

    -
  • tableheader
    87.9

    89.9

    96
  • tableheader
    -

    -

    -
  • tableheader
    89.7

    91.2

    96
  • tableheader
    89.7

    90.9

    94
  • tableheader
    -

    -

    -
  • tableheader
    69.2

    78.6

    -
  • tableheader
    -

    -

    85
  • tableheader
    -

    -

    74
  • tableheader
    57.9

    65.8

    75
  • tableheader
    -

    -

    -
  • tableheader
    37

    48.3

    49
  • tableheader
    52.5

    65

    -
  • tableheader
    30.3

    39

    56
  • tableheader
    -

    -

    -
  • tableheader
    42.3

    56.6

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    43
  • tableheader
    -

    -

    44
  • tableheader
    32.4

    47

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 GBE1 - Q04446
2 PRPF8 - Q6P2Q9
 

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 = 12 nM 9809715 502835 22037378
Lestaurtinib Kd = 13 nM 126565 22037378
Sunitinib Kd = 59 nM 5329102 535 19654408
Staurosporine Kd = 73 nM 5279 22037378
N-Benzoylstaurosporine Kd = 80 nM 56603681 608533 19654408
AT9283 IC50 > 100 nM 24905142 19143567
SU14813 Kd = 120 nM 10138259 1721885 22037378
K-252a; Nocardiopsis sp. IC50 > 150 nM 3813 281948 22037377
TG101348 Kd = 170 nM 16722836 1287853 22037378
KW2449 Kd = 200 nM 11427553 1908397 22037378
Tozasertib Kd = 240 nM 5494449 572878 22037378
Aloisine A IC50 > 250 nM 5326843 75680 22037377
Dovitinib Kd = 250 nM 57336746 22037378
Cdk1/2 Inhibitor III IC50 = 500 nM 5330812 261720 22037377
Compound 52 IC50 = 500 nM 2856 22037377
AZ960 IC50 < 700 nM 25099184 18775810
BCP9000906 IC50 > 1 µM 5494425 21156 22037377
GSK-3 Inhibitor XIII IC50 > 1 µM 6419766 359482 22037377
IDR E804 IC50 > 1 µM 6419764 1802727 22037377
MK5108 IC50 > 1 µM 24748204 20053775
NU6140 IC50 > 1 µM 10202471 1802728 22037377
SB218078 IC50 > 1 µM 447446 289422 22037377
Silmitasertib IC50 > 1 µM 24748573 21174434
SNS314 IC50 > 1 µM 16047143 514582 18678489
SU6656 IC50 > 1 µM 5353978 605003 22037377
TBCA IC50 > 1 µM 1095828 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
A674563 Kd = 1.5 µM 11314340 379218 22037378
PHA-665752 Kd = 1.6 µM 10461815 450786 22037378
Ruboxistaurin Kd = 1.6 µM 153999 91829 22037378
CHEMBL248757 Ki > 1.736 µM 44444843 248757 17935989
Momelotinib IC50 > 2 µM 25062766 19295546
Axitinib Kd = 2.3 µM 6450551 1289926 22037378
NVP-TAE684 Kd = 2.9 µM 16038120 509032 22037378
Ruxolitinib Kd = 3.3 µM 25126798 1789941 22037378
CHEMBL1240703 Kd = 3.5 µM 52945601 1240703 19654408
Bosutinib Kd = 3.9 µM 5328940 288441 22037378
JNJ-28871063 IC50 > 4 µM 17747413 17975007
 

Disease Linkage

General Disease Association:

Musculoskeletal disorders
Specific Diseases (Non-cancerous):

Centronuclear myopathy
Comments:
In animal studies, mice lacking MSSK1 display a type 2 fibre-specific myopathy characterized by an increase portion of cells with centrally placed nuclei. In addition, overexpressing SRPK3 in mice leads to severe muscle degeneration and lethality.
 
Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for MSSK1 in diverse human cancers of 688, which is 1.5-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 161 for this protein kinase in human cancers was 2.7-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: 0.06 % in 24914 diverse cancer specimens. This rate is only -25 % 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: 0.21 % in 1270 large intestine cancers tested; 0.19 % in 589 stomach cancers tested; 0.17 % in 864 skin cancers tested; 0.16 % in 603 endometrium cancers tested; 0.1 % in 942 upper aerodigestive tract cancers tested; 0.1 % in 1822 lung cancers tested; 0.07 % in 548 urinary tract cancers tested; 0.07 % in 273 cervix cancers tested; 0.06 % in 1316 breast cancers tested; 0.05 % in 1512 liver cancers tested; 0.03 % in 558 thyroid cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.03 % in 1276 kidney cancers tested; 0.02 % in 881 prostate cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:

None > 3 in 20,197 cancer specimens
Comments:
Only 5 deletions, 1 insertion and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
SRPK3
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