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Updated November 2019

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Nomenclature

Short Name:
CDKL4
Full Name:
Cyclin-dependent kinase-like 4
Alias:
  • AA626859

Classification

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

Specific Links

Entrez-Gene Entry: 344387
Entrez-Protein Entry: NP_001009565
GeneCards Entry: CDKL4
Pfam Entry: Q5MAI5
PhosphoNET Entry: Q5MAI5
Phosphosite Plus Entry: 7.3845e+006
Source Entry: CDKL4
UCSD-Nature Entry: A003846
UniProt Entry: Q5MAI5

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):
36,223
# Amino Acids:
315
# mRNA Isoforms:
2
mRNA Isoforms:
43,384 Da (379 AA; Q5MAI5); 36,223 Da (315 AA; Q5MAI5-2)
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
4 286 Pkinase
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K33.
Tyrosine phosphorylated:

Y160+.
 

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
    -

    -

    -

    -

  • adrenal
    0.4

    3

    3

    1

  • bladder
    -

    -

    -

    -

  • brain
    0.3

    2

    3

    2

  • breast
    0.3

    2

    3

    0

  • cervix
  • colon
    0.1

    1

    3

    0

  • heart
    0.1

    1

    3

    0

  • intestine
    0.1

    1

    3

    0

  • kidney
    0.1

    1

    3

    0

  • liver
    0.3

    2

    3

    1

  • lung
    0.3

    2

    3

    1

  • lymphnode
    -

    -

    -

    -

  • ovary
    0.3

    2

    3

    0

  • pancreas
    0.1

    1

    3

    0

  • pituitary
    -

    -

    -

    -

  • prostate
    0.3

    2

    3

    1

  • salivarygland
    0.1

    1

    3

    0

  • skeletalmuscle"
    0.4

    3

    3

    2

  • skin
    0.3

    2

    3

    1

  • spinalcord
    0.1

    1

    3

    1

  • spleen
    0.1

    1

    3

    1

  • stomach
    -

    -

    -

    -

  • testis
    0.9

    7

    3

    1

  • thymus
    0.6

    5

    3

    6

  • thyroid
    0.1

    1

    3

    1

  • tonsil
    0.3

    2

    3

    0

  • trachea
    0.1

    1

    3

    0

  • uterus
    0.3

    2

    3

    0

  • reticulocytes"
    -

    -

    -

    -

  • t-lymphocytes
    100

    790

    12

    53

  • b-lymphocytes
    -

    -

    -

    -

  • neutrophils
    -

    -

    -

    -

  • macrophages
    -

    -

    -

    -

  • sperm
    8

    64

    9

    59

 

Evolution

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

    100

    100
  • tableheader
    0

    0

    97
  • tableheader
    79.8

    81.2

    95
  • tableheader
    -

    -

    94
  • tableheader
    -

    -

    -
  • tableheader
    80.3

    83.1

    93
  • tableheader
    -

    -

    -
  • tableheader
    83.3

    90

    91
  • tableheader
    62.7

    76.6

    90
  • tableheader
    -

    -

    -
  • tableheader
    62.5

    75.8

    -
  • tableheader
    38.4

    57.4

    -
  • tableheader
    38

    60

    -
  • tableheader
    64

    77.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    38.7

    51.5

    -
  • tableheader
    51.4

    67

    -
  • tableheader
    53.8

    70.5

    -
  • tableheader
    56.4

    71

    -
  • tableheader
    -

    -

    -
  • tableheader
    35.8

    56.8

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
Likely that phosphorylation at Tyr-160 is required for catalytic activity based on homology with other CDK's.
Inhibition:
Likely that phosphorylation at Tyr-15 is inhibitory based on homology with other CDK's.
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
 

Disease Linkage

Comments:
The low rate of reported somatic mutations, but broad and multi-site in CDKL4 indicates that it may function as a tumour requiring protein (TRP) in human tumours.
 
Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for CDKL4 in diverse human cancers of 350, 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: 0.07 % in 24726 diverse cancer specimens. This rate is only -13 % 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: 0.32 % in 603 endometrium cancers tested; 0.22 % in 864 skin cancers tested.
Frequency of Mutated Sites:

None > 3 in 20,009 cancer specimens
Comments:
Only 1 insertion, and no deletions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
CDKL4
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