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Updated November 2019

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Nomenclature

Short Name:
MPSK1
Full Name:
Serine-threonine-protein kinase 16
Alias:
  • EC 2.7.11.1
  • HPSK
  • TGF-beta stimulated factor 1
  • TSF1
  • MPSK
  • PKL12
  • Serine,threonine protein kinase 16
  • STK16

Classification

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

Specific Links

Entrez-Gene Entry: 8576
Entrez-Protein Entry: NP_003682
GeneCards Entry: MPSK
KinBASE Entry: MPSK1
OMIM Entry: 604719
Pfam Entry: O75716
PhosphoNET Entry: O75716
Phosphosite Plus Entry: 762
Protein Data Bank Entry: 2BUJ
ScanSite Entry: O75716
Source Entry: STK16
UCSD-Nature Entry: A003028
UniProt Entry: O75716

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):
34656
# Amino Acids:
305
# mRNA Isoforms:
1
mRNA Isoforms:
34,656 Da (305 AA; O75716)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
2BUJ

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
20 292 Pkinase
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Myristoylated:
G2.
Palmitoylated:
C6,C8.
Serine phosphorylated:

S197-.
Threonine phosphorylated:

T185.
Tyrosine phosphorylated:

Y198-.
Ubiquitinated:
K102.
 

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
    77

    1017

    13

    1101

  • adrenal
    20

    262

    12

    284

  • bladder
    3

    44

    1

    0

  • brain
    30

    402

    48

    668

  • breast
    46

    605

    14

    585

  • cervix
    2

    33

    37

    13

  • colon
    22

    285

    19

    515

  • heart
    100

    1321

    21

    2222

  • intestine
    22

    287

    10

    248

  • kidney
    7

    99

    47

    69

  • liver
    7

    89

    14

    42

  • lung
    47

    622

    86

    656

  • lymphnode
    5

    63

    14

    17

  • ovary
    6

    76

    9

    125

  • pancreas
    4

    54

    12

    95

  • pituitary
    5

    70

    10

    32

  • prostate
    2

    33

    100

    27

  • salivarygland
    3

    46

    9

    39

  • skeletalmuscle"
    4

    53

    55

    105

  • skin
    29

    388

    58

    414

  • spinalcord
    6

    74

    11

    54

  • spleen
    4

    53

    12

    28

  • stomach
    6

    78

    2

    46

  • testis
    7

    92

    12

    90

  • thymus
    4

    56

    12

    30

  • thyroid
    55

    722

    29

    983

  • tonsil
    5

    72

    17

    28

  • trachea
    4

    50

    10

    43

  • uterus
    5

    61

    9

    67

  • reticulocytes"
    7

    89

    14

    74

  • t-lymphocytes
    51

    679

    18

    461

  • b-lymphocytes
    43

    573

    17

    562

  • neutrophils
    0.9

    12

    17

    9

  • macrophages
    69

    905

    26

    743

  • sperm
    5

    71

    13

    21

 

Evolution

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

    100

    100
  • tableheader
    99.7

    99.7

    100
  • tableheader
    99

    99.7

    99
  • tableheader
    -

    -

    92
  • tableheader
    -

    -

    96
  • tableheader
    95.7

    97

    96
  • tableheader
    -

    -

    -
  • tableheader
    94.1

    97.7

    94
  • tableheader
    95.4

    97.4

    95
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    68.2

    82.3

    68
  • tableheader
    69.8

    84.9

    68
  • tableheader
    -

    -

    66
  • tableheader
    -

    -

    -
  • tableheader
    39.1

    58.8

    42
  • tableheader
    40.6

    63.2

    -
  • tableheader
    -

    -

    -
  • tableheader
    39.7

    64.6

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    38
  • tableheader
    -

    -

    39
  • tableheader
    27.5

    45.9

    36
  • tableheader
    -

    -

    39
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 NCK1 - P16333
3 RAF1 - P04049
4 PXN - P49023
5 SYN1 - P17600
6 ARHGEF6 - Q15052
7 GIT1 - Q9Y2X7
8 PRMT5 - O14744
9 PAK2 - Q13177
10 NCK2 - O43639
11 CDC42 - P60953
12 RAC3 - P60763
13 RAC2 - P15153
 

Regulation

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

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
MPSK1 O75716 T185 EGSRQALTLQDWAAQ
MPSK1 O75716 S197 AAQRCTISYRAPELF -
MPSK1 O75716 Y198 AQRCTISYRAPELFS -
 

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
DRG1 Q9Y295 T101 YEFTTLTTVPGVIRY
MPSK1 (STK16) O75716 S197 AAQRCTISYRAPELF -
MPSK1 (STK16) O75716 T185 EGSRQALTLQDWAAQ
MPSK1 (STK16) O75716 Y198 AQRCTISYRAPELFS -
Sarcolipin O00631 T5 MGINTRELFLNF___
 

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
R406 Kd = 1.7 nM 11984591 22037378
TG101348 Kd = 6.6 nM 16722836 1287853 22037378
Hesperadin Kd < 10 nM 10142586 514409 19035792
JNJ-28312141 Kd = 18 nM 22037378
Nintedanib Kd = 18 nM 9809715 502835 22037378
Lestaurtinib Kd = 19 nM 126565 22037378
LKB1(AAK1 dual inhibitor) Kd = 24 nM 44588117 516312 19035792
KW2449 Kd = 29 nM 11427553 1908397 22037378
CHEMBL249097 Kd < 50 nM 25138012 249097 19035792
IDR E804 IC50 > 50 nM 6419764 1802727 22037377
JNJ-7706621 Kd = 140 nM 5330790 191003 18183025
AC1O6ZUA Kd = 150 nM 6539569 408019 19035792
GSK-3 Inhibitor XIII IC50 > 150 nM 6419766 359482 22037377
PKR Inhibitor IC50 > 150 nM 6490494 235641 22037377
Tozasertib Kd < 150 nM 5494449 572878 19035792
Staurosporine Kd = 200 nM 5279 15711537
CHEMBL1082152 Kd = 230 nM 11560568 1082152 20138512
BML-275 IC50 > 250 nM 11524144 478629 22037377
Cdk1/2 Inhibitor III IC50 > 250 nM 5330812 261720 22037377
IRAK-1-4 Inhibitor I IC50 > 250 nM 11983295 379787 22037377
JAK3 Inhibitor VI IC50 > 250 nM 16760524 22037377
K-252a; Nocardiopsis sp. IC50 > 250 nM 3813 281948 22037377
NU6140 IC50 > 250 nM 10202471 1802728 22037377
Pazopanib IC50 > 250 nM 10113978 477772 22037377
Sunitinib Kd = 250 nM 5329102 535 18183025
N-Benzoylstaurosporine Kd = 280 nM 56603681 608533 18183025
Axitinib Kd = 370 nM 6450551 1289926 22037378
Ruxolitinib Kd = 490 nM 25126798 1789941 22037378
Aloisine A IC50 = 500 nM 5326843 75680 22037377
Dovitinib IC50 = 500 nM 57336746 22037377
Flt-3 Inhibitor II IC50 = 500 nM 11601743 377193 22037377
Indirubin-3′-monoxime IC50 = 500 nM 5326739 22037377
1;9-Pyrazoloanthrone Kd = 510 nM 8515 7064 15711537
Aurora A Inhibitor 23 (DF) Kd < 600 nM 21992004
SU14813 Kd = 730 nM 10138259 1721885 18183025
NVP-TAE684 Kd = 800 nM 16038120 509032 22037378
Aloisine; RP106 IC50 > 1 µM 44350092 126343 22037377
Amgen TBK 1 inhibitor (Compound II) IC50 = 1 µM
Febuxostat IC50 = 1 µM 134018 1164729
GSK-3 Inhibitor IX IC50 > 1 µM 5287844 409450 22037377
SB218078 IC50 > 1 µM 447446 289422 22037377
VEGFR2 Kinase Inhibitor IV IC50 > 1 µM 5329468 92461 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
BI2536 Kd = 1.1 µM 11364421 513909 22037378
AC1NS4N8 Kd < 1.25 µM 5353854 101797 19035792
CHEMBL511337 Kd < 1.25 µM 44588220 511337 19035792
IKK-2 Inhibitor IV Kd < 1.25 µM 9903786 257167 19035792
PLX4720 Kd = 1.9 µM 24180719 1230020 22037378
Enzastaurin Kd = 2.5 µM 176167 300138 22037378
SureCN373973 Kd < 2.5 µM 9818573 30678 19035792
TTT-3002 IC50 > 3 µM
SureCN4875304 IC50 > 3.5 µM 46871765 20472445
PP242 Kd = 4 µM 25243800 22037378
Staurosporine aglycone IC50 < 4 µM 3035817 281948
PHA-665752 Kd = 4.8 µM 10461815 450786 22037378
 

Disease Linkage

General Disease Association:

Infectious disease
Specific Diseases (Non-cancerous):

Cryptococcosis; Diffuse Mesangial sclerosis (DMS)
Comments:
Cryptococcosis has a relation to the disorders of meningitis and systemic lupus erythematosus. Cryptococcosis is characterized by an infection with a fungus leading to the development of symptoms that include fatigue, fever, confusion, headache, blurred vision, and a dry cough. The disorder can take several weeks for the full display of symptoms, and it can affect the lung, the liver, and T cells. Diffuse Mesangial Sclerosis (DMS) is a rare disorder that has been related to the nephrotic and denysdrash syndromes. DMS may be characterized by proteinuria (protein in urine), hypoalbuminemia (low albumin levels in blood), and edema (accumulation of fluid in the interstitium under the skin). Myristoylation of MPSK1 can be inhibited with a G2A mutation, while palmitoylation can be lost with either a C6S or C8S mutation.
 
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 human T-cell prolymphocytic leukemia (%CFC= +120, p<0.004).
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: 0.05 % in 24433 diverse cancer specimens. This rate is only -32 % 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: 0.27 % in 603 endometrium cancers tested; 0.24 % in 1229 large intestine cancers tested; 0.18 % in 555 stomach cancers tested; 0.18 % in 548 urinary tract cancers tested; 0.12 % in 273 cervix cancers tested; 0.12 % in 1608 lung cancers tested; 0.11 % in 864 skin cancers tested; 0.07 % in 1512 liver cancers tested; 0.06 % in 558 thyroid cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.04 % in 807 ovary cancers tested; 0.03 % in 1289 breast cancers tested; 0.03 % in 1253 kidney cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R50Q (4).
Comments:
No deletions, insertions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
STK16_ENST00000409638
OMIM Entry:
604719
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