Nomenclature
Short Name:
PIK3R4
Full Name:
Phosphoinositide 3-kinase regulatory subunit 4
Alias:
- EC 2.7.11.1
- Kinase kinase PIK3R4
- P150
- Phosphoinositide-3-kinase, regulatory subunit 4
- PI3R4
- VPS15
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
VPS15
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
153103
# Amino Acids:
1358
# mRNA Isoforms:
1
mRNA Isoforms:
153,103 Da (1358 AA; Q99570)
4D Structure:
Heterodimer. This subunit, part of a complex composed of regulatory and catalytic subunits, associates with the phosphatidylinositol 3-kinase type 3 (PIK3C3). Forms a complex with BECN1, PIK3C3 and either UVRAG and KIAA0226/Rubicon, or with KIAA0831/Barkor. In this complex, presence of UVRAG and KIAA0831/Barkor are mutually exclusive.
1D Structure:
Subfamily Alignment
Domain Distribution:
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K951.
Myristoylated:
G2.
Serine phosphorylated:
S115, S740, S808, S813, S814, S853, S861, S865, S892, S894, S925, S1074, S1079, S1289.
Threonine phosphorylated:
T61, T116, T543, T555, T680, T927, T942, T1283, T1316.
Tyrosine phosphorylated:
Y673, Y1272, Y1290, Y1291.
Ubiquitinated:
K68, K97, K280, K309, K449, K553, K773, K791, K850, K888, K951, K1293, K1307.
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:
79
739
42
967
4
38
20
44
4
37
3
57
61
576
115
1681
62
584
34
594
7
65
118
113
12
110
43
235
93
869
38
1338
54
502
24
457
6
53
99
59
6
52
26
51
60
565
221
542
4
38
36
50
5
45
14
49
3
29
17
31
6
57
22
79
4
34
121
36
3
25
12
17
5
45
111
59
47
437
162
551
5
46
15
58
5
48
20
53
6
59
14
34
6
59
14
59
4
39
16
43
100
938
66
1743
4
36
39
44
4
42
12
37
4
34
14
43
4
36
42
43
74
693
30
800
50
470
51
489
19
174
111
595
74
691
83
654
9
87
48
63
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.9
99.9
100
-
-
99.5
-
-
97
-
-
-
97.8
98.8
98
-
-
-
95.9
97.9
96
95.7
97.8
96
-
-
-
88.7
94
-
91.4
95.4
92
-
-
87
82.3
90
84
-
-
-
43.5
63
45
48.1
64.7
-
-
-
29
-
-
-
-
-
-
-
-
-
-
-
33
-
-
40
24.8
46.1
33
-
-
38
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | PIK3C3 - Q8NEB9 |
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
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Ovarian cancer
Comments:
PIK3R4 might be an oncoprotein (OP). Activating mutations in PIK3R4 have been recently discovered in certain types of cancer cell. Somatic mutations are associated with metastatic melanoma, and primary ovarian cancer predict patient outcome.
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: Brain glioblastomas (%CFC= -68, p<0.001); Oral squamous cell carcinomas (OSCC) (%CFC= +94, p<0.0002); and Uterine leiomyomas (%CFC= -66, p<0.054). The COSMIC website notes an up-regulated expression score for PIK3R4 in diverse human cancers of 783, which is 1.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 172 for this protein kinase in human cancers was 2.9-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 25524 diverse cancer specimens. This rate is only -10 % 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: 0.28 % in 1270 large intestine cancers tested; 0.26 % in 864 skin cancers tested; 0.21 % in 603 endometrium cancers tested; 0.21 % in 589 stomach cancers tested; 0.19 % in 548 urinary tract cancers tested; 0.16 % in 1634 lung cancers tested; 0.12 % in 1512 liver cancers tested; 0.07 % in 710 oesophagus cancers tested; 0.07 % in 1316 breast cancers tested; 0.06 % in 891 ovary cancers tested; 0.05 % in 273 cervix cancers tested; 0.04 % in 1276 kidney cancers tested; 0.03 % in 1467 pancreas cancers tested; 0.02 % in 939 prostate cancers tested; 0.02 % in 382 soft tissue cancers tested; 0.01 % in 958 upper aerodigestive tract cancers tested; 0.01 % in 2103 central nervous system cancers tested; 0 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R936Q (4); R1189H (3); R1189C (2).
Comments:
Only 2 deletions, no insertions, and 3 complex mutations are noted on the COSMIC website.