Nomenclature
Short Name:
PIK3CB
Full Name:
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform kinase p110 subunit beta; PIK3C1; PK3CB; PtdIns-3-kinase p110
Alias:
- Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform kinase p110 subunit beta
- PIK3C1
- PK3CB
- PtdIns-3-kinase p110
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
PIKK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
122762
# Amino Acids:
1070
# mRNA Isoforms:
1
mRNA Isoforms:
122,762 Da (1070 AA; P42338)
4D Structure:
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S115, S416, S423, S520, S724, S947, S1070.
Threonine phosphorylated:
T113, T417, T427, T721, T961.
Tyrosine phosphorylated:
Y244, Y246, Y425, Y436, Y503, Y504, Y505, Y772, Y962.
Ubiquitinated:
K230, K514, K828, K886, K1025.
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:
25
687
32
857
2
45
17
35
3
69
23
53
17
458
112
661
27
726
25
662
9
245
82
544
15
392
35
493
25
665
62
1481
24
650
17
577
5
146
109
105
2
59
47
46
19
527
188
587
3
87
45
78
1
28
15
21
4
107
21
114
2
48
16
32
9
233
279
2201
6
162
34
153
4
120
104
117
25
687
109
723
5
124
40
105
3
78
44
65
4
116
25
91
2
66
34
52
4
113
40
95
21
581
73
661
3
76
48
76
3
94
34
82
2
67
34
57
2
67
28
45
22
595
24
543
100
2703
42
6327
6
171
72
449
40
1088
52
784
5
132
35
117
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
56.5
72.9
100
99.6
99.9
100
-
-
97
-
-
-
97.2
98.8
97
-
-
-
95.2
97
96
95.8
97.8
96
-
-
-
81.1
85.3
-
86.6
93.6
87
23.6
41.3
78
65.5
79.7
69
-
-
-
-
-
-
46.6
65.6
-
26.4
47.8
-
42.9
63.6
-
-
-
-
-
-
-
-
-
-
22.7
38.6
-
23.4
41.9
-
-
-
-
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 |
|---|
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
Specific Cancer Types:
Breast cancer; Oral sqaumous cell carcinomas
Comments:
PIK3CB appears to be an oncoprotein (OP). The PI3K pathway is often mutated in cancers, leading to overactivation of intracellular signalling pathways and the inappropriate promotion of cell growth, proliferation, and motility. An activating mutation in the PIK3CB helical domain (a E633K substitution) has been observed in HER2-positive breast cancer cell lines. The E633K mutation increases kinase phosphotransferase activity of PIK3CB, but apparently has no measurable effect on protein-protein interactions. In addition, the E633K mutation can also abolish the need for a Ras-binding protein for PIK3CB activation, indicating a gain-of-function mutation to produces an oncogenic protein. Consistent with this, expression of the mutant PIK3CB protein in cancer cells is associated with increased activation of Akt and S6K1, as well as increased transformation, chemotaxis, proliferation, and survival. In addition, significantly elevated levels of PIK3CB expression were observed in late stages of oral squamous cell carcinomas. Furthermore, the PIK3CB protein displayed a highly significant direct interaction with K-Ras, indicating that both pathways are activated in the late stages of the cancer and possibly interact with one another.
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= +81, p<0.03); Brain glioblastomas (%CFC= +91, p<0.101); Breast epithelial carcinomas (%CFC= +51, p<0.046); Prostate cancer (%CFC= -47, p<0.104); and Prostate cancer - primary (%CFC= +102, p<0.0001). The COSMIC website notes an up-regulated expression score for PIK3CB in diverse human cancers of 648, which is 1.4-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 66 for this protein kinase in human cancers was 1.1-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: 0.07 % in 25430 diverse cancer specimens. This rate is only -8 % lower and is very similar 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: 0.27 % in 864 skin cancers tested; 0.22 % in 603 endometrium cancers tested; 0.2 % in 1240 large intestine cancers tested; 0.16 % in 569 stomach cancers tested; 0.12 % in 1634 lung cancers tested; 0.11 % in 1512 liver cancers tested; 0.08 % in 238 bone cancers tested; 0.08 % in 1078 upper aerodigestive tract cancers tested; 0.07 % in 273 cervix cancers tested; 0.07 % in 1475 breast cancers tested; 0.06 % in 441 autonomic ganglia cancers tested; 0.06 % in 1345 kidney cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.05 % in 548 urinary tract cancers tested; 0.05 % in 2074 central nervous system cancers tested; 0.04 % in 865 ovary cancers tested; 0.04 % in 1467 pancreas cancers tested; 0.03 % in 939 prostate cancers tested; 0.03 % in 558 thyroid cancers tested; 0.02 % in 382 soft tissue cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: L832W (5); R321Q (5); R628Q (3); V927A (3).
Comments:
Only 2 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.