Nomenclature
Short Name:
WEE1
Full Name:
Wee1-like protein kinase
Alias:
- EC 2.7.10.2
- Kinase WEE1
- WEE1
- WEE1A
- WEE1hu
Classification
Type:
Dual specificity protein kinase
Group:
Other
Family:
WEE
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
71,597
# Amino Acids:
646
# mRNA Isoforms:
2
mRNA Isoforms:
71,597 Da (646 AA; P30291);49,072 Da (432 AA; P30291-2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 299 | 569 | Pkinase |
| 577 | 612 | Coiled-coil |
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S48, S53-, S67, S85, S121-, S123-, S127, S137, S139, S150, S165, S193-, S196, S211, S212, S242, S262, S270, S293, S307, S312+, S444, S471+, S472, S480, S571, S576, S642-.
Threonine phosphorylated:
T49, T69, T173, T187-, T190-, T217, T239.
Tyrosine phosphorylated:
Y132, Y258, Y272, Y646.
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:
100
1923
31
3304
2
47
17
47
76
1452
12
912
40
775
94
2737
57
1103
25
750
7
133
81
135
19
373
35
561
45
872
45
922
27
523
17
512
9
165
96
276
14
274
35
420
38
736
186
705
14
274
34
457
3
54
15
50
10
186
28
321
2
43
16
31
17
321
208
2415
12
236
21
301
9
165
93
280
37
710
109
753
10
191
27
318
13
250
31
361
26
498
22
584
32
616
23
646
28
544
27
714
55
1049
59
910
19
364
37
533
35
678
23
787
54
1030
23
1160
7
131
28
111
30
571
24
536
84
1616
36
3600
48
929
67
1568
36
692
57
662
63
1219
35
2216
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.5
99.8
99.5
42.1
56.2
99
-
-
-
-
-
94
70.9
71.4
97
-
-
-
90.6
92.7
91
91.6
93.2
92
-
-
-
72.8
79.3
-
80.2
85.9
81
42.9
55.3
73
64.2
75.1
70
-
-
-
36.5
54.2
49
41.6
59.3
-
-
-
-
39.6
55.6
-
-
-
-
-
-
-
-
-
-
23.1
38.9
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | CDC2 - P06493 |
| 2 | FBXW11 - Q9UKB1 |
| 3 | YWHAB - P31946 |
| 4 | CASP3 - P42574 |
| 5 | CRK - P46108 |
| 6 | CSNK2A1 - P68400 |
| 7 | CDK2 - P24941 |
| 8 | PIN1 - Q13526 |
| 9 | BRSK2 - Q8IWQ3 |
| 10 | BRSK1 - Q8TDC3 |
| 11 | CDCA3 - Q99618 |
| 12 | SKP2 - Q13309 |
| 13 | BTRC - Q9Y297 |
| 14 | PLK1 - P53350 |
| 15 | BRD8 - Q9H0E9 |
Regulation
Activation:
NA
Inhibition:
Phosphorylatio of Ser-121 induces proteolysis through interaction with BTRC and FBW1B. Phosphorylation of Ser-53 and Ser-123 beta-transducin repeat-containing protein recognition for degradation by ubiquitination. Phosphorylation of Thr-187, Thr-190 and Ser-193 induces proteolysis through interaction with BTRC and FBW1B. Phosphorylation of Ser-642 inhibits phosphotransferase activity and induces interaction with 14-3-3 theta.
Synthesis:
Synthesis is increased during S and G2 phases, presumably by an increase in transcription;
Degradation:
Protein levels fall in M phase as a result of decreased synthesis combined with degradation.
Known Upstream Kinases
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
| Kinase Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
| PLK1 | P53350 | S53 | GHSTGEDSAFQEPDS | - |
| CK2a1 | P68400 | S121 | WEEEGFGSSSPVKSP | - |
| CDK1 | P06493 | S123 | EEGFGSSSPVKSPAA | - |
| CK2a1 | P68400 | T187 | RKLRLFDTPHTPKSL | - |
| CK2a1 | P68400 | T190 | RLFDTPHTPKSLLSK | - |
| CK2a1 | P68400 | S193 | DTPHTPKSLLSKARG | - |
| BRSK1 | Q8TDC3 | S642 | KKMNRSVSLTIY___ | - |
| Akt1 | P31749 | S642 | KKMNRSVSLTIY___ | - |
| BRSK2 | Q8IWQ3 | S642 | KKMNRSVSLTIY___ | - |
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 |
|---|
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 |
|---|
Disease Linkage
General Disease Association:
Cancer, immune disorders
Specific Diseases (Non-cancerous):
Suppurative lymphadenitis
Specific Cancer Types:
Leukemia, Ovarian; Pancreatic
Comments:
WEE1 kinase is a target for cancer therapy. Specific inhibition of WEE1 kinase can be used to increase the sensitivity of T-cell leukemia and pancreatic cancer. WEE1 was found to be a novel independent prognostic marker of poor survival ovarian carcinomas.
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= +82, p<(0.0003); Brain glioblastomas (%CFC= -73, p<0.0002); Breast epithelial carcinomas (%CFC= -62, p<0.034); Cervical cancer (%CFC= +100, p<0.0001); Colon mucosal cell adenomas (%CFC= +71, p<(0.0003); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +78, p<0.011); T-cell prolymphocytic leukemia (%CFC= +62, p<0.03); Uterine leiomyomas (%CFC= -73, p<0.08); Uterine leiomyomas from fibroids (%CFC= -57, p<0.01); and Vulvar intraepithelial neoplasia (%CFC= +99, p<0.043). The COSMIC website notes an up-regulated expression score for WEE1 in diverse human cancers of 396, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 17 for this protein kinase in human cancers was 0.3-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: 0.05 % in 25403 diverse cancer specimens. This rate is only -29 % 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 1270 large intestine cancers tested; 0.23 % in 548 urinary tract cancers tested; 0.13 % in 589 stomach cancers tested; 0.1 % in 895 skin cancers tested; 0.1 % in 603 endometrium cancers tested; 0.08 % in 1512 liver cancers tested; 0.06 % in 1956 lung cancers tested; 0.05 % in 942 upper aerodigestive tract cancers tested; 0.05 % in 1491 breast cancers tested; 0.04 % in 1467 pancreas cancers tested; 0.03 % in 939 prostate cancers tested; 0.02 % in 891 ovary cancers tested; 0.02 % in 710 oesophagus cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.02 % in 1276 kidney cancers tested; 0.01 % in 2082 central nervous system cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: K255R (4); K255E (2); E587K (3).
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.