Nomenclature
Short Name:
PIK3CG
Full Name:
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Alias:
- 5-bisphosphate 3-kinase catalytic subunit, gamma isoform
- PI3KG1
- PI3Kgamma
- PI3-kinase p110 subunit gamma
- PK3CG; PtdIns-3-kinase p110
- EC 2.7.1.153
- P11G
- Phosphatidylinositol-4; Phosphoinositide-3-kinase, catalytic, gamma polypeptide
- PI3K
- PI3K p110-gamma
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
126454
# Amino Acids:
1101
# mRNA Isoforms:
1
mRNA Isoforms:
126,454 Da (1102 AA; P48736)
4D Structure:
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K1000.
Serine phosphorylated:
S227, S230, S582, S620, S636, S853, S1101.
Threonine phosphorylated:
T228, T229, T232, T250, T607, T627, T746, T1024.
Tyrosine phosphorylated:
Y757.
Ubiquitinated:
K606.
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:
34
749
29
1068
0.4
8
15
8
2
36
11
61
22
493
98
1733
19
425
23
374
12
278
82
978
7
148
31
371
87
1949
47
3992
14
311
17
278
0.7
16
78
24
1
24
31
44
22
483
152
474
4
85
34
131
0.5
12
12
10
0.5
12
15
13
0.1
3
15
3
0.7
16
119
23
26
576
21
2457
0.4
9
87
11
12
264
109
305
2
37
23
51
4
96
27
124
2
42
22
61
2
52
21
52
5
112
23
133
100
2230
62
5148
4
81
37
98
22
485
21
2057
1
24
21
41
0.9
21
28
18
34
766
24
734
17
385
36
397
5
110
68
280
31
691
57
627
5
118
35
113
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.8
99.9
100
98.8
99.5
99
-
-
95
-
-
-
92.1
95.3
92
-
-
-
94
96.7
94
31.3
51.6
94
-
-
-
31.3
51
-
84.6
91
85
20.5
39.8
80
71.8
84.3
48
-
-
-
-
-
-
-
-
-
25.7
47.2
-
-
-
-
-
-
-
-
-
-
-
-
-
22.7
39.8
-
22.8
41.2
-
-
-
-
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:
Meningiomas; Adenocarcinomas
Comments:
PIK3CG is linked to Meningiomas, which are a rare disorders characterized by slow-growing benign brain tumours. Meningiomas will arise from the meninges (protective barrier around the brain) and can lead to thickening of the skull.
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 human Cervical cancer stage 2A (%CFC= +75, p<0.078). The COSMIC website notes an up-regulated expression score for PIK3CG in diverse human cancers of 259, which is 0.6-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 2 for this protein kinase in human cancers was 97% 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. The inflammatory response via PIK3CG can be reduced, with a K833R mutation. A R947P mutation can result in the complete inhibition of lipid or protein kinase phosphotransferase activity of PIK3CG, and yet not inhibit complex formation between PIK3CG and ADRBK1.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.16 % in 25561 diverse cancer specimens. This rate is 2.1-fold higher 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: 0.66 % in 895 skin cancers tested; 0.6 % in 1240 large intestine cancers tested; 0.48 % in 1634 lung cancers tested; 0.4 % in 569 stomach cancers tested; 0.35 % in 603 endometrium cancers tested; 0.21 % in 1184 upper aerodigestive tract cancers tested; 0.17 % in 710 oesophagus cancers tested; 0.13 % in 1512 liver cancers tested; 0.12 % in 1467 pancreas cancers tested; 0.11 % in 2103 central nervous system cancers tested; 0.1 % in 548 urinary tract cancers tested; 0.1 % in 273 cervix cancers tested; 0.09 % in 1496 breast cancers tested; 0.07 % in 939 prostate cancers tested; 0.07 % in 127 biliary tract cancers tested; 0.06 % in 865 ovary cancers tested; 0.06 % in 1345 kidney cancers tested; 0.04 % in 238 bone cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: A84V (6); V759I (6); A156V (5); V274I (4).
Comments:
Only 1 deletion and 1 insertion and no complex mutations are noted on the COSMIC website.