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Updated November 2019

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Nomenclature

Short Name:
DCAMKL1
Full Name:
Serine-threonine-protein kinase DCAMKL1
Alias:
  • DCAK1
  • DCDC3A
  • EC 2.7.11.1
  • KIAA0369
  • Kinase DCAMKL1
  • DCLK
  • DCLK1
  • Doublecortin- like and CAM kinase-like 1
  • Doublecortin-like kinase 1

Classification

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

Specific Links

Entrez-Gene Entry: 9201
Entrez-Protein Entry: NP_004725
GeneCards Entry: DCLK1
OMIM Entry: 604742
PhosphoNET Entry: O15075
Phosphosite Plus Entry: 811
Protein Data Bank Entry: 1MFW
ScanSite Entry: O15075
Source Entry: DCLK1
UniProt Entry: O15075
Kinexus Products: DCAMKL1
GYS1 (2-11) KinSub - Glycogen synthase (muscle)-derived (P2-S11, rabbit) peptide; CaMK2 protein kinase substrate - Powder PE-01ACW95
DCAMKLSubtide - DCAMKL2 protein kinase substrate peptide - Powder PE-01BHA90

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):
82,224
# Amino Acids:
740
# mRNA Isoforms:
4
mRNA Isoforms:
82,224 Da (740 AA; O15075); 81,100 Da (729 AA; O15075-2); 47,681 Da (433 AA; O15075-4); 46,557 Da (422 AA; O15075-3)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
5JZJ

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
57 143 DCX1
186 269 DCX2
67 158 DCX
390 647 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ GYS1 (2-11) KinSub - Glycogen synthase (muscle)-derived (P2-S11, rabbit) peptide; CaMK2 protein kinase substrate - Powder PE-01ACW95
○ DCAMKLSubtide - DCAMKL2 protein kinase substrate peptide - Powder PE-01BHA90
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Methylated:
R712 (M2).
Serine phosphorylated:

S32, S164, S172, S274, S305, S307, S312, S313, S327, S330, S332, S334, S337, S340, S352, S353, S489, S683, S729, S738.
Threonine phosphorylated:

T34, T46, T324, T336, T678, T687, T732.
Tyrosine phosphorylated:

Y265, Y493, Y725.
 

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

    1226

    44

    1365

  • adrenal
    14

    229

    19

    637

  • bladder
    5

    81

    14

    69

  • brain
    61

    967

    164

    1039

  • breast
    53

    843

    44

    653

  • cervix
    45

    710

    100

    2458

  • colon
    10

    158

    55

    351

  • heart
    25

    403

    52

    620

  • intestine
    17

    276

    17

    222

  • kidney
    5

    73

    137

    207

  • liver
    2

    33

    40

    75

  • lung
    29

    470

    215

    532

  • lymphnode
    6

    89

    38

    94

  • ovary
    12

    193

    16

    563

  • pancreas
    5

    76

    34

    205

  • pituitary
    8

    121

    28

    302

  • prostate
    11

    172

    281

    1989

  • salivarygland
    41

    654

    26

    2886

  • skeletalmuscle"
    6

    103

    133

    401

  • skin
    47

    755

    167

    658

  • spinalcord
    61

    972

    35

    2351

  • spleen
    4

    63

    35

    55

  • stomach
    3

    51

    16

    42

  • testis
    20

    312

    27

    747

  • thymus
    4

    65

    33

    103

  • thyroid
    65

    1042

    99

    2192

  • tonsil
    3

    41

    40

    44

  • trachea
    8

    132

    26

    249

  • uterus
    14

    230

    26

    536

  • reticulocytes"
    5

    75

    56

    53

  • t-lymphocytes
    16

    248

    24

    250

  • b-lymphocytes
    100

    1594

    48

    3966

  • neutrophils
    9

    140

    116

    438

  • macrophages
    35

    550

    104

    473

  • sperm
    5

    74

    61

    61

 

Evolution

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

    100

    100
  • tableheader
    79.5

    80.2

    0
  • tableheader
    79.5

    80.2

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    65.4

    77.5

    100
  • tableheader
    99.9

    99.9

    -
  • tableheader
    -

    -

    98
  • tableheader
    96.4

    97.3

    98
  • tableheader
    65.3

    77.8

    -
  • tableheader
    86.2

    88

    -
  • tableheader
    86.2

    88

    97
  • tableheader
    63.7

    65

    -
  • tableheader
    -

    -

    -
  • tableheader
    24.7

    35

    -
  • tableheader
    -

    -

    42
  • tableheader
    29.8

    47.6

    -
  • tableheader
    -

    -

    45
  • tableheader
    52.3

    66

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    33
  • tableheader
    -

    -

    38
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).
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
NVP-TAE684 Kd = 4.9 nM 16038120 509032 22037378
Aurora A Inhibitor 1 (DF) Kd < 50 nM 21992004
Ruxolitinib Kd = 68 nM 25126798 1789941 22037378
Aurora A Inhibitor 23 (DF) Kd < 100 nM 21992004
Staurosporine Kd = 110 nM 5279 18183025
TG101348 Kd = 190 nM 16722836 1287853 22037378
Aurora A Inhibitor 29 (DF) Kd < 200 nM 21992004
XMD8-92 IC50 = 300 nM 46843772 1673046 20832753
Crizotinib Kd = 330 nM 11626560 601719 22037378
Sunitinib Kd = 370 nM 5329102 535 18183025
Nintedanib Kd = 540 nM 9809715 502835 22037378
Lestaurtinib Kd = 550 nM 126565 18183025
SU14813 Kd = 550 nM 10138259 1721885 18183025
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
PHA-665752 Kd = 1.4 µM 10461815 450786 22037378
AC1NS7CD Kd = 1.6 µM 5329665 295136 22037378
SNS032 Kd = 1.6 µM 3025986 296468 18183025
KW2449 Kd = 2 µM 11427553 22037378
Alvocidib Kd = 2.1 µM 9910986 428690 18183025
GSK690693 Kd = 2.4 µM 16725726 494089 22037378
JNJ-7706621 Kd = 2.5 µM 5330790 191003 18183025
GSK1838705A Kd = 4.1 µM 25182616 464552 22037378
 

Disease Linkage

Comments:
DCAMKL1 has been found to mark tumour stem cells in the polyps of Apc(Min/+) heterozygous mice, but not normal stem cells.
 
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: Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +170, p<0.103); Clear cell renal cell carcinomas (cRCC) (%CFC= +172, p<0.004); Prostate cancer - metastatic (%CFC= -54, p<0.0001); Prostate cancer - primary (%CFC= +74, p<0.0001); Skin melanomas - malignant (%CFC= -62, p<0.01); Skin squamous cell carcinomas (%CFC= -58, p<0.087); and Vulvar intraepithelial neoplasia (%CFC= -49, p<0.011). The COSMIC website notes an up-regulated expression score for DCAMKL1 in diverse human cancers of 381, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than 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: 0.17 % in 24794 diverse cancer specimens. This rate is 2.3-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: 2.7 % in 10 peritoneum cancers tested; 0.84 % in 1271 large intestine cancers tested; 0.59 % in 864 skin cancers tested; 0.4 % in 603 endometrium cancers tested; 0.36 % in 710 oesophagus cancers tested; 0.21 % in 127 biliary tract cancers tested; 0.17 % in 1634 lung cancers tested; 0.16 % in 1512 liver cancers tested; 0.14 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R60C (8); R93Q (4).
Comments:
Only 6 deletions, 1 insertion and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
DCLK1
OMIM Entry:
604742
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