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Updated November 2019

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Nomenclature

Short Name:
CLIK1
Full Name:
Serine-threonine-protein kinase 35
Alias:
  •  CLP-36 interacting kinase
  • BA550O8.2
  • PDLIM1-interacting kinase 1
  • Serine/threonine kinase 35
  • STK35
  • Clik1
  • CLP-36 interacting kinase
  • CLP-36-interacting kinase
  • EC 2.7.11.1

Classification

Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NKF4
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 140901
Entrez-Protein Entry: NP_543026
GeneCards Entry: CLIK1
KinBASE Entry: CLIK1.
OMIM Entry: 609370
Pfam Entry: Q8TDR2
PhosphoNET Entry: Q8TDR2
Phosphosite Plus Entry: 2207
ScanSite Entry: Q8TDR2
Source Entry: STK35
UCSD-Nature Entry: A003844
UniProt Entry: Q8TDR2

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):
58051
# Amino Acids:
534
# mRNA Isoforms:
1
mRNA Isoforms:
58,051 Da (534 AA; Q8TDR2)
4D Structure:
Interacts with PDLIM1/CLP-36.
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
202 529 Pkinase
 

Post-translation Modifications

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

S6, S34, S203, S212, S413, S414, S418, S456, S499.
Threonine phosphorylated:

T458, T465, T496.
Tyrosine phosphorylated:

Y202, Y213, Y217.
Ubiquitinated:
K503.
 

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
    71

    1370

    36

    1219

  • adrenal
    26

    509

    12

    822

  • bladder
    -

    -

    -

    -

  • brain
    10

    185

    132

    329

  • breast
    42

    819

    46

    596

  • cervix
    5

    96

    45

    155

  • colon
    9

    165

    57

    285

  • heart
    60

    1161

    16

    2329

  • intestine
    0.4

    8

    3

    2

  • kidney
    10

    195

    95

    369

  • liver
    22

    424

    13

    756

  • lung
    36

    702

    62

    692

  • lymphnode
    21

    410

    4

    250

  • ovary
    50

    966

    7

    1074

  • pancreas
    16

    316

    13

    438

  • pituitary
    5

    100

    29

    139

  • prostate
    25

    493

    117

    3815

  • salivarygland
    26

    496

    7

    620

  • skeletalmuscle"
    10

    187

    67

    431

  • skin
    39

    753

    137

    647

  • spinalcord
    8

    155

    13

    221

  • spleen
    2

    31

    9

    46

  • stomach
    -

    -

    -

    -

  • testis
    100

    1934

    11

    1902

  • thymus
    8

    146

    13

    196

  • thyroid
    51

    982

    91

    964

  • tonsil
    13

    255

    7

    307

  • trachea
    28

    532

    7

    669

  • uterus
    18

    351

    7

    381

  • reticulocytes"
    8

    146

    42

    179

  • t-lymphocytes
    91

    1751

    12

    23

  • b-lymphocytes
    6

    109

    35

    87

  • neutrophils
    20

    379

    97

    650

  • macrophages
    46

    880

    130

    742

  • sperm
    24

    470

    74

    447

 

Evolution

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

    100

    100
  • tableheader
    74.9

    75

    99
  • tableheader
    74.7

    75

    97
  • tableheader
    -

    -

    98.5
  • tableheader
    -

    -

    -
  • tableheader
    83.3

    84.8

    91
  • tableheader
    -

    -

    -
  • tableheader
    87.3

    90.5

    88
  • tableheader
    -

    -

    88
  • tableheader
    -

    -

    -
  • tableheader
    49.4

    63.1

    -
  • tableheader
    -

    -

    87
  • tableheader
    41.7

    51.3

    91
  • tableheader
    43

    53.1

    80
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 BMPR1B - O00238
 

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
Bosutinib Kd = 2 nM 5328940 288441 22037378
Cediranib Kd = 5.4 nM 9933475 491473 22037378
SU14813 Kd = 8.2 nM 10138259 1721885 22037378
AST-487 Kd = 16 nM 11409972 574738 22037378
Brivanib Kd = 26 nM 11234052 377300 22037378
Vandetanib Kd = 56 nM 3081361 24828 22037378
Staurosporine Kd = 140 nM 5279 22037378
Foretinib Kd = 230 nM 42642645 1230609 22037378
NVP-TAE684 Kd = 260 nM 16038120 509032 22037378
PD173955 Kd = 360 nM 447077 386051 22037378
Alvocidib Kd = 450 nM 9910986 428690 22037378
PP242 Kd = 500 nM 25243800 22037378
Crizotinib Kd = 610 nM 11626560 601719 22037378
KW2449 Kd = 630 nM 11427553 22037378
Dasatinib Kd = 770 nM 11153014 1421 22037378
Lestaurtinib Kd = 810 nM 126565 22037378
Nintedanib Kd = 810 nM 9809715 502835 22037378
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Sunitinib Kd = 1.3 µM 5329102 535 19654408
R406 Kd = 1.4 µM 11984591 22037378
Canertinib Kd = 2.9 µM 156414 31965 22037378
JNJ-28312141 Kd = 3.2 µM 22037378
Neratinib Kd = 4.5 µM 9915743 180022 22037378
 

Disease Linkage

Comments:
CLIK1 levels are up-regulated 1-8-fold in human tumours compared to most other protein kinases.
 
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= +98, p<0.073); and Ovary adenocarcinomas (%CFC= -96, p<0.0002). The COSMIC website notes an up-regulated expression score for CLIK1 in diverse human cancers of 849, which is 1.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 102 for this protein kinase in human cancers was 1.7-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: 0.04 % in 24726 diverse cancer specimens. This rate is -45 % 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: 0.19 % in 1270 large intestine cancers tested; 0.1 % in 1634 lung cancers tested; 0.09 % in 1512 liver cancers tested.
Frequency of Mutated Sites:

None > 4 in 20,010 cancer specimens
Comments:
Only 1 insertion, and no deletions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
STK35
OMIM Entry:
609370
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