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Updated November 2019

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Nomenclature

Short Name:
HIPK4
Full Name:
Homeodomain interacting protein kinase 4
Alias:
  • BG105231
  • FLJ32818

Classification

Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
DYRK
SubFamily:
HIPK
 
 

Specific Links

Entrez-Gene Entry: 147746
Entrez-Protein Entry: NP_653286
KinBASE Entry: HIPK4
Pfam Entry: Q8NE63
PhosphoNET Entry: Q8NE63
Phosphosite Plus Entry: 3761
UCSD-Nature Entry: A003847
UniProt Entry: Q8NE63
Kinexus Products: HIPK4
DYRKtide KinSub - DYR peptide substrate - Powder PE-01ACQ95

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):
69,425
# Amino Acids:
616
# mRNA Isoforms:
1
mRNA Isoforms:
69,425 Da (616 AA; Q8NE63)
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
11 347 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ DYRKtide KinSub - DYR peptide substrate - Powder PE-01ACQ95
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K19, K27.
Serine phosphorylated:

S301.
Threonine phosphorylated:

T122, T381, T390+.
Tyrosine phosphorylated:

Y175+, Y392, Y393.
 

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

    2218

    6

    984

  • adrenal
    0.8

    18

    4

    5

  • bladder
    -

    -

    -

    -

  • brain
    3

    60

    28

    77

  • breast
    30

    676

    10

    466

  • cervix
    0.7

    16

    9

    9

  • colon
    0.5

    12

    13

    11

  • heart
    6

    129

    5

    150

  • intestine
    0.4

    9

    3

    1

  • kidney
    9

    198

    5

    314

  • liver
    5

    115

    5

    148

  • lung
    35

    786

    11

    657

  • lymphnode
    -

    -

    -

    -

  • ovary
    0.1

    3

    3

    1

  • pancreas
    6

    127

    5

    172

  • pituitary
    2

    36

    5

    7

  • prostate
    5

    102

    9

    183

  • salivarygland
    1

    26

    3

    1

  • skeletalmuscle"
    0.7

    15

    3

    1

  • skin
    23

    507

    26

    241

  • spinalcord
    5

    113

    5

    137

  • spleen
    5

    120

    5

    163

  • stomach
    -

    -

    -

    -

  • testis
    0.9

    19

    3

    4

  • thymus
    5

    116

    5

    151

  • thyroid
    29

    649

    19

    577

  • tonsil
    0.4

    8

    3

    2

  • trachea
    3

    67

    3

    8

  • uterus
    0.5

    10

    3

    2

  • reticulocytes"
    -

    -

    -

    -

  • t-lymphocytes
    25

    544

    12

    43

  • b-lymphocytes
    8

    174

    5

    16

  • neutrophils
    0.2

    4

    12

    0

  • macrophages
    40

    888

    26

    765

  • sperm
    19

    412

    22

    261

 

Evolution

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

    100

    100
  • tableheader
    98.2

    98.8

    98
  • tableheader
    97.4

    98

    -
  • tableheader
    -

    -

    88
  • tableheader
    -

    -

    -
  • tableheader
    89.4

    91.7

    90
  • tableheader
    -

    -

    -
  • tableheader
    87.1

    90

    87
  • tableheader
    86.5

    89.9

    87
  • tableheader
    -

    -

    -
  • tableheader
    47.8

    53.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    23.1

    34.2

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

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

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
p53 (TP53) P04637 S9 EEPQSDPSVEPPLSQ
 

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Kinections GIF
Matrix Type:
Derived from alignment of 30 peptides phosphorylated by recombinant HIPK4 in vitro tested in-house by Kinexus.
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
Foretinib Kd = 510 pM 42642645 1230609 22037378
Sorafenib Kd = 2.7 nM 216239 1336 19654408
AST-487 Kd = 3.9 nM 11409972 574738 22037378
Linifanib Kd = 46 nM 11485656 223360 22037378
Barasertib Kd = 97 nM 16007391 215152 22037378
Bosutinib Kd = 130 nM 5328940 288441 22037378
Lestaurtinib Kd = 150 nM 126565 22037378
SB218078 IC50 > 150 nM 447446 289422 22037377
Sunitinib Kd = 160 nM 5329102 535 19654408
TG101348 Kd = 220 nM 16722836 1287853 22037378
Gefitinib Kd = 310 nM 123631 939 22037378
Quizartinib Kd = 320 nM 24889392 576982 19654408
NVP-TAE684 Kd = 350 nM 16038120 509032 22037378
Afatinib Kd = 360 nM 10184653 1173655 22037378
Staurosporine Kd = 390 nM 5279 22037378
Tandutinib Kd = 400 nM 3038522 124660 19654408
Cdk1/2 Inhibitor III IC50 = 500 nM 5330812 261720 22037377
RAF265 Kd = 560 nM 11656518 558752 22037378
Momelotinib IC50 < 750 nM 25062766 19295546
A674563 Kd = 760 nM 11314340 379218 22037378
N-Benzoylstaurosporine Kd = 950 nM 56603681 608533 19654408
Erlotinib Kd = 960 nM 176870 553 22037378
SU14813 Kd = 970 nM 10138259 1721885 22037378
A 443654 IC50 < 1 µM 10172943 379300 19465931
AG1478 IC50 > 1 µM 2051 7917 22037377
JAK3 Inhibitor VI IC50 > 1 µM 16760524 22037377
JNJ-7706621 IC50 > 1 µM 5330790 191003 22037377
K-252a; Nocardiopsis sp. IC50 > 1 µM 3813 281948 22037377
KW2449 Kd = 1 µM 11427553 1908397 22037378
SU11652 IC50 > 1 µM 24906267 13485 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Canertinib Kd = 1.1 µM 156414 31965 22037378
Enzastaurin Kd = 1.2 µM 176167 300138 22037378
GSK1838705A Kd = 1.2 µM 25182616 464552 22037378
Nintedanib Kd = 1.2 µM 9809715 502835 22037378
PHA-665752 Kd = 1.3 µM 10461815 450786 22037378
Neratinib Kd = 1.5 µM 9915743 180022 22037378
Alvocidib Kd = 2 µM 9910986 428690 22037378
BI2536 Kd = 2 µM 11364421 513909 22037378
R406 Kd = 2.8 µM 11984591 22037378
Crizotinib Kd = 3.6 µM 11626560 601719 22037378
 

Disease Linkage

Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for HIPK4 in diverse human cancers of 392, which is 0.9-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: 0.06 % in 24726 diverse cancer specimens. This rate is only -15 % 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: 0.28 % in 864 skin cancers tested; 0.28 % in 589 stomach cancers tested; 0.24 % in 603 endometrium cancers tested; 0.21 % in 548 urinary tract cancers tested; 0.19 % in 1270 large intestine cancers tested; 0.18 % in 273 cervix cancers tested; 0.08 % in 1634 lung cancers tested; 0.08 % in 1459 pancreas cancers tested; 0.07 % in 881 prostate cancers tested; 0.07 % in 238 bone cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.05 % in 2082 central nervous system cancers tested; 0.04 % in 1316 breast cancers tested; 0.03 % in 942 upper aerodigestive tract cancers tested; 0.03 % in 1512 liver cancers tested; 0.02 % in 833 ovary cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R278C (3).
Comments:
Only 2 deletions, and no insertions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
HIPK4
OMIM Entry:
611712
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