Nomenclature
Short Name:
HUNK
Full Name:
Hormonally up-regulated neu tumor-associated kinase
Alias:
- B19
- EC 2.7.11.1
- MAK-V
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMKL
SubFamily:
HUNK
Structure
Mol. Mass (Da):
79,686
# Amino Acids:
714
# mRNA Isoforms:
1
mRNA Isoforms:
79,686 Da (714 AA; P57058)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 62 | 320 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K674.
Serine phosphorylated:
S65, S360, S368.
Threonine phosphorylated:
T618.
Tyrosine phosphorylated:
Y378, Y388, Y406+.
Ubiquitinated:
K483.
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:
89
1466
19
1318
2
26
9
26
5
90
10
130
10
158
79
292
35
575
21
414
1
17
46
10
1.2
19
25
14
100
1640
27
3855
13
215
10
207
3
53
44
80
3
49
24
78
39
641
81
550
2
30
22
39
2
35
6
43
7
108
21
142
0.9
15
12
12
37
602
92
3170
19
304
14
1025
3
41
46
25
27
436
79
380
3
49
19
63
2
37
19
43
3
47
12
80
2
34
15
41
5
75
18
144
58
953
51
2146
3
44
25
104
6
98
15
295
4
61
16
63
12
202
14
65
28
459
18
320
44
720
26
1662
10
170
65
409
48
792
52
682
4
66
35
52
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.7
99.9
100
26.2
46.5
99
-
-
92
-
-
-
78.6
83.1
91
-
-
-
92.4
95.9
92
24.6
44.7
92
-
-
-
35.7
54.6
-
26.7
43.4
69
64.6
76.9
67
23.4
36.6
-
-
-
-
-
-
-
-
-
-
21.6
34.6
-
30
45.2
-
26.3
43.3
-
-
-
-
-
-
-
25.9
43.3
-
24.9
42.7
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | RABEP1 - Q15276 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
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 |
|---|
| SU14813 | Kd = 3.7 nM | 10138259 | 1721885 | 22037378 |
| N-Benzoylstaurosporine | Kd = 240 nM | 56603681 | 608533 | 22037378 |
| NVP-TAE684 | Kd = 350 nM | 16038120 | 509032 | 22037378 |
| Dovitinib | Kd = 410 nM | 57336746 | 22037378 | |
| KW2449 | Kd = 460 nM | 11427553 | 1908397 | 22037378 |
| Sunitinib | Kd = 500 nM | 5329102 | 535 | 22037378 |
| Lestaurtinib | Kd = 570 nM | 126565 | 22037378 | |
| Staurosporine | Kd = 620 nM | 5279 | 22037378 | |
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| PHA-665752 | Kd = 1.4 µM | 10461815 | 450786 | 22037378 |
| Axitinib | Kd = 1.5 µM | 6450551 | 1289926 | 22037378 |
| Vandetanib | Kd = 4.1 µM | 3081361 | 24828 | 22037378 |
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Breast cancer
Comments:
HUNK may be an oncoprotein (OP). Higher metastastive potential has been shown in HUNK-expressing tumours in Myc-induced mouse tumours. Human breast cancers with HUNK-wildtype tumours showed a higher probability of metastasis, recurrence, and poorer prognosis than HUNK-deficient tumours.
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: Bladder carcinomas (%CFC= -47, p<0.007); Brain glioblastomas (%CFC= +1229, p<0.01); Colon mucosal cell adenomas (%CFC= +78, p<0.01); Malignant pleural mesotheliomas (MPM) tumours (%CFC= -47, p<0.013); and Ovary adenocarcinomas (%CFC= +64, p<0.031). The COSMIC website notes an up-regulated expression score for HUNK in diverse human cancers of 413, 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: 0.08 % in 24729 diverse cancer specimens. This rate is very similar (+ 8% higher) to 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: 0.45 % in 864 skin cancers tested; 0.29 % in 589 stomach cancers tested; 0.28 % in 603 endometrium cancers tested; 0.24 % in 1270 large intestine cancers tested; 0.18 % in 1636 lung cancers tested; 0.15 % in 548 urinary tract cancers tested; 0.08 % in 710 oesophagus cancers tested; 0.08 % in 1512 liver cancers tested; 0.06 % in 238 bone cancers tested; 0.06 % in 1459 pancreas cancers tested; 0.05 % in 273 cervix cancers tested; 0.04 % in 1316 breast cancers tested; 0.04 % in 1276 kidney cancers tested; 0.03 % in 943 upper aerodigestive tract cancers tested; 0.03 % in 441 autonomic ganglia cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.02 % in 881 prostate cancers tested; 0.02 % in 833 ovary cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,012 cancer specimens
Comments:
Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.