64637
Pathway
Phospholipase C Signaling Pathway
Phospholipase C pathways is one of the major intracellular signalling pathways regulating hormones. It functions to activate inositol lipid signalling pathways causing the hydrolysis of PIP2 by PLC to IP3 and diacylglycerol to activate protein kinase C. IP3 releases calcium from the endoplasmic reticulum. PIP3 is an important regulator of AKT signaling and downstream pathways.
Protein
PW064775
Center
PathwayVisualizationContext65051
1800
1410
#000099
PathwayVisualization64521
64637
Phospholipase C Signaling Pathway
Phospholipase C pathways is one of the major intracellular signalling pathways regulating hormones. It functions to activate inositol lipid signalling pathways causing the hydrolysis of PIP2 by PLC to IP3 and diacylglycerol to activate protein kinase C. IP3 releases calcium from the endoplasmic reticulum. PIP3 is an important regulator of AKT signaling and downstream pathways.
Protein
1
57770
MAPK pathway
ActivatingSubPathway
229920
22403074
Gresset A, Sondek J, Harden TK: The phospholipase C isozymes and their regulation. Subcell Biochem. 2012;58:61-94. doi: 10.1007/978-94-007-3012-0_3.
64637
Pathway
229921
25658460
Smrcka AV: Regulation of phosphatidylinositol-specific phospholipase C at the nuclear envelope in cardiac myocytes. J Cardiovasc Pharmacol. 2015 Mar;65(3):203-10. doi: 10.1097/FJC.0000000000000195.
64637
Pathway
229923
https://cgap.nci.nih.gov/Pathways/BioCarta/h_plcPathway
64637
Pathway
1
Cell
CL:0000000
5
Hepatocyte
CL:0000182
4
Cardiomyocyte
CL:0000746
3
Neuron
CL:0000540
7
Epithelial Cell
CL:0000066
2
Platelet
CL:0000233
8
Beta cell
CL:0000639
1
Homo sapiens
9606
Eukaryote
Human
2
Bacteria
2
Prokaryote
Bacteria
3
Escherichia coli
562
Prokaryote
12
Mus musculus
10090
Eukaryote
Mouse
5
Bos taurus
9913
Eukaryote
Cattle
17
Rattus norvegicus
10116
Eukaryote
Rat
19
Schizosaccharomyces pombe
4896
Eukaryote
24
Solanum lycopersicum
4081
Eukaryote
Tomato
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
21
Xenopus laevis
8355
Eukaryote
African clawed frog
6
Caenorhabditis elegans
6239
Eukaryote
Roundworm
25
Escherichia coli (strain K12)
83333
Prokaryote
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
10
Drosophila melanogaster
7227
Eukaryote
Fruit fly
23
Pseudomonas aeruginosa
287
Prokaryote
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
62
Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)
62977
Prokaryote
5
Cytoplasm
GO:0005737
6
Lysosome
GO:0005764
4
Peroxisome
GO:0005777
3
Mitochondrial Matrix
GO:0005759
2
Mitochondrion
GO:0005739
10
Cell Membrane
GO:0005886
11
Extracellular Space
GO:0005615
16
Lysosomal Lumen
GO:0043202
7
Endoplasmic Reticulum Membrane
GO:0005789
1
Cytosol
GO:0005829
18
Melanosome Membrane
GO:0033162
13
Endoplasmic Reticulum
GO:0005783
25
Golgi apparatus
GO:0005794
14
Mitochondrial Outer Membrane
GO:0005741
12
Mitochondrial Inner Membrane
GO:0005743
20
Endoplasmic Reticulum Lumen
GO:0005788
21
Synapse
GO:0045202
15
Nucleus
GO:0005634
31
Periplasmic Space
GO:0005620
35
Chloroplast
GO:0009507
36
Membrane
GO:0016020
53
Endoplasmic Reticulum Body
GO:0010168
34
Plant-Type Vacuole
GO:0000325
40
Periplasm
GO:0042597
19
sarcoplasmic reticulum
GO:0016529
24
Mitochondrial Intermembrane Space
GO:0005758
32
Inner Membrane
GO:0070258
1
Liver
BTO:0000759
72
9
4
Adrenal Medulla
BTO:0000049
71
8
25
Intestine
BTO:0000648
28
Stomach
BTO:0001307
155
26
7
Nervous System
BTO:0001484
8
Blood Vessel
BTO:0001102
74
11
11
Heart
BTO:0000562
73
10
2
Endothelium
BTO:0000393
5
cardiocyte
BTO:0001539
18
Pancreas
BTO:0000988
24
Brain
BTO:0000142
89
16
8
5
1
1
PW_BS000008
9
6
1
1
PW_BS000009
5
4
1
1
PW_BS000005
4
3
1
1
PW_BS000004
3
2
1
1
PW_BS000003
14
10
1
PW_BS000014
13
1
2
1
PW_BS000013
15
11
1
PW_BS000015
28
1
16
1
1
PW_BS000028
10
1
7
1
1
PW_BS000010
20
4
1
1
1
PW_BS000020
33
18
1
1
PW_BS000033
18
13
1
1
PW_BS000018
2
1
1
1
PW_BS000002
31
1
5
1
1
PW_BS000031
49
7
1
1
PW_BS000049
54
1
3
1
5
PW_BS000054
43
25
1
1
PW_BS000043
24
4
10
1
1
PW_BS000024
22
14
1
1
PW_BS000022
60
25
1
PW_BS000060
46
1
1
4
PW_BS000046
17
12
1
1
PW_BS000017
29
1
1
1
PW_BS000029
70
28
5
1
1
PW_BS000070
72
5
1
3
PW_BS000072
61
25
1
7
PW_BS000061
36
1
20
1
1
PW_BS000036
37
7
21
1
3
PW_BS000037
93
25
20
1
1
PW_BS000093
27
15
1
PW_BS000027
7
1
1
PW_BS000007
97
1
5
2
1
PW_BS000097
100
5
2
1
PW_BS000100
94
3
PW_BS000094
103
3
3
1
PW_BS000103
105
11
3
PW_BS000105
111
5
12
1
PW_BS000111
113
6
12
1
PW_BS000113
112
2
12
1
PW_BS000112
110
2
3
1
PW_BS000110
123
1
7
5
1
PW_BS000123
125
13
5
1
PW_BS000125
126
6
5
1
PW_BS000126
127
1
16
5
1
PW_BS000127
130
13
12
1
PW_BS000130
114
11
12
PW_BS000114
129
1
5
12
1
PW_BS000129
135
5
17
1
PW_BS000135
118
1
17
1
PW_BS000118
108
1
3
PW_BS000108
6
1
3
1
PW_BS000006
140
10
3
PW_BS000140
101
5
3
1
PW_BS000101
143
1
5
19
1
PW_BS000143
146
5
19
1
PW_BS000146
107
31
3
PW_BS000107
95
1
7
2
1
PW_BS000095
147
1
24
1
PW_BS000147
151
1
4
1
PW_BS000151
155
3
24
1
PW_BS000155
157
2
24
1
PW_BS000157
161
3
18
1
PW_BS000161
163
2
18
1
PW_BS000163
159
24
PW_BS000159
1
1
PW_BS000001
166
1
1
PW_BS000166
178
3
21
1
PW_BS000178
180
2
21
1
PW_BS000180
152
8
4
PW_BS000152
117
1
3
1
PW_BS000117
188
1
18
PW_BS000024
160
1
18
1
PW_BS000160
205
5
6
1
PW_BS000024
207
6
6
1
PW_BS000024
206
2
6
1
PW_BS000024
211
10
18
PW_BS000024
213
7
18
1
PW_BS000024
214
25
18
1
PW_BS000024
215
6
18
1
PW_BS000024
198
5
18
1
PW_BS000024
216
4
18
1
PW_BS000024
210
13
18
1
PW_BS000024
212
1
7
18
1
PW_BS000024
222
3
4
1
PW_BS000024
224
2
4
1
PW_BS000024
190
11
18
PW_BS000024
170
18
PW_BS000170
225
35
4
1
PW_BS000024
226
4
4
1
PW_BS000024
162
12
18
1
PW_BS000162
26
1
1
1
5
PW_BS000026
277
1
2
18
PW_BS000024
164
4
PW_BS000164
281
1
25
1
PW_BS000024
285
10
4
1
PW_BS000024
286
36
4
1
PW_BS000024
287
53
4
1
PW_BS000024
249
13
4
1
PW_BS000024
227
34
4
1
PW_BS000024
65
11
1
PW_BS000065
290
5
49
1
PW_BS000024
291
6
49
1
PW_BS000024
292
4
49
1
PW_BS000024
298
1
7
10
1
PW_BS000024
300
13
10
1
PW_BS000024
301
6
10
1
PW_BS000024
302
1
16
10
1
PW_BS000024
223
12
4
1
PW_BS000024
294
11
4
1
PW_BS000024
308
10
1
1
PW_BS000024
315
1
23
PW_BS000024
318
31
23
PW_BS000024
322
1
23
1
PW_BS000024
293
4
1
PW_BS000024
253
5
4
1
PW_BS000024
132
1
12
1
PW_BS000132
133
3
12
1
PW_BS000133
134
12
12
1
PW_BS000134
331
7
12
1
PW_BS000028
332
1
7
12
1
PW_BS000028
333
1
2
12
PW_BS000028
115
10
12
PW_BS000115
334
4
12
1
PW_BS000028
336
1
12
1
PW_BS000028
337
1
16
12
1
PW_BS000028
341
4
1
12
1
PW_BS000028
343
18
12
1
PW_BS000028
347
1
3
12
5
PW_BS000028
329
14
12
1
PW_BS000028
352
25
12
PW_BS000028
353
25
12
7
PW_BS000028
356
25
12
1
PW_BS000028
360
4
10
12
1
PW_BS000028
368
3
60
1
PW_BS000028
370
2
60
1
PW_BS000028
228
36
1
PW_BS000024
119
2
17
1
PW_BS000119
383
7
5
1
PW_BS000100
384
12
5
1
PW_BS000100
390
7
6
1
PW_BS000112
391
12
6
1
PW_BS000112
398
7
17
1
PW_BS000113
232
40
3
PW_BS000024
122
5
5
1
PW_BS000122
406
3
5
1
PW_BS000115
407
2
5
1
PW_BS000115
408
4
5
1
PW_BS000115
124
1
5
1
PW_BS000124
412
1
2
5
PW_BS000115
405
10
5
PW_BS000115
409
11
5
PW_BS000115
415
18
5
1
PW_BS000115
414
1
5
5
1
PW_BS000115
425
1
3
5
5
PW_BS000115
429
1
5
1
PW_BS000115
121
12
17
1
PW_BS000121
419
25
5
1
PW_BS000115
434
4
10
5
1
PW_BS000115
382
14
5
1
PW_BS000100
436
25
5
PW_BS000115
120
3
17
1
PW_BS000120
374
4
17
1
PW_BS000053
443
6
17
1
PW_BS000115
446
1
2
17
PW_BS000115
376
10
17
PW_BS000053
137
11
17
PW_BS000137
447
1
7
17
1
PW_BS000115
136
13
17
1
PW_BS000136
448
1
16
17
1
PW_BS000115
451
18
17
1
PW_BS000115
450
1
5
17
1
PW_BS000115
460
1
3
17
5
PW_BS000115
464
1
17
1
PW_BS000115
455
25
17
1
PW_BS000115
469
4
10
17
1
PW_BS000115
399
14
17
1
PW_BS000113
471
25
17
PW_BS000115
472
25
17
7
PW_BS000115
297
5
10
1
PW_BS000024
479
3
10
1
PW_BS000115
481
2
10
1
PW_BS000115
482
4
10
1
PW_BS000115
299
1
10
1
PW_BS000024
483
11
10
PW_BS000115
478
10
10
PW_BS000115
487
18
10
1
PW_BS000115
490
25
10
1
PW_BS000115
495
7
10
1
PW_BS000115
484
14
10
1
PW_BS000115
480
12
10
1
PW_BS000115
501
3
6
1
PW_BS000115
502
4
6
1
PW_BS000115
388
1
6
1
PW_BS000112
208
11
6
PW_BS000024
209
10
6
PW_BS000024
504
18
6
1
PW_BS000115
507
25
6
1
PW_BS000115
515
4
10
6
1
PW_BS000115
389
14
6
1
PW_BS000112
395
13
6
1
PW_BS000113
513
1
7
6
1
PW_BS000115
16
2
1
2
PW_BS000016
21
5
1
1
4
PW_BS000021
35
5
19
1
4
PW_BS000035
47
19
1
4
PW_BS000047
42
24
1
1
PW_BS000042
58
1
14
1
1
PW_BS000058
71
11
1
3
PW_BS000071
66
18
5
1
8
PW_BS000066
345
24
12
1
PW_BS000028
74
1
3
PW_BS000074
51
8
1
PW_BS000051
418
24
5
1
PW_BS000115
454
24
17
1
PW_BS000115
489
24
10
1
PW_BS000115
506
24
6
1
PW_BS000115
168
32
1
PW_BS000168
23
15
1
1
PW_BS000023
89
2
PW_BS000089
653
1
62
4
PW_BS000508
665
18
1
8
PW_BS000508
87
24
5
1
1
PW_BS000087
48
PW_B000048
123
7622
ProteinComplex
1
124
7621
ProteinComplex
1
1420
Water
HMDB0002111
Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).
7732-18-5
C00001
962
15377
937
O
H2O
InChI=1S/H2O/h1H2
XLYOFNOQVPJJNP-UHFFFAOYSA-N
water
18.0153
18.010564686
1
water
0
0
FDB013390
Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;Wasser
PW_C001420
H2O
55
8
94
9
109
5
139
4
151
3
162
14
481
13
526
15
624
28
652
10
691
20
770
33
823
18
838
2
1094
31
1377
49
1465
54
1590
43
2018
24
2532
22
2678
60
2727
46
2778
17
2805
29
3143
70
3164
72
3634
61
4598
36
4727
37
4941
93
5030
27
5156
7
5195
97
5214
100
5227
94
5236
103
5297
105
5319
111
5343
113
5355
112
5402
110
5470
123
5483
125
5492
126
5507
127
5534
130
5537
114
5541
129
5591
135
5608
118
5622
108
5691
6
5759
140
5778
101
5841
143
5853
146
5877
107
5890
95
5910
147
5940
151
6032
155
6059
157
6087
161
6123
163
6133
159
6215
1
6218
166
6477
178
6507
180
6600
152
6713
117
6840
188
6888
160
7162
205
7181
207
7193
206
7211
211
7228
213
7238
214
7243
215
7295
198
7350
216
7388
210
7401
212
7467
222
7492
224
7500
190
7588
170
8201
225
8237
226
8414
162
9265
26
11850
277
11922
164
12011
281
12213
285
12250
286
12264
287
12327
249
12520
227
12632
65
12693
290
12705
291
12715
292
13007
298
13019
300
13025
301
13037
302
13261
223
13327
294
15340
308
42327
315
42695
318
43691
322
76914
293
77019
253
77102
132
77131
133
77215
134
77378
331
77397
332
77471
333
77516
115
77536
334
77628
336
77722
337
77759
341
77816
343
77982
347
78071
329
78235
352
78242
353
78270
356
79113
360
80014
368
80039
370
80591
228
80656
119
93830
383
94794
384
110557
390
110639
391
115844
398
119879
232
119915
122
119963
406
120008
407
120046
408
120113
124
120365
412
120430
405
120438
409
120606
415
120794
414
121158
425
121240
429
121351
121
121381
419
121607
434
122118
382
122384
436
122753
120
122797
374
122804
443
123012
446
123064
376
123072
137
123131
447
123142
136
123162
448
123231
451
123384
450
123730
460
123810
464
123940
455
124165
469
124670
399
124938
471
124945
472
125305
297
125353
479
125386
481
125424
482
125480
299
125682
483
125707
478
125745
487
126054
490
126238
495
126273
484
126764
480
126896
501
126963
502
127017
388
127177
208
127199
209
127227
504
127506
507
127576
515
127836
389
128082
395
128176
513
353
Calcium
HMDB0000464
Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.
14127-61-8
C00076
271
29108
CA%2b2
266
DB01373
[Ca++]
Ca
InChI=1S/Ca/q+2
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
calcium(2+) ion
40.078
39.962591155
0
calcium(2+) ion
2
2
FDB003513
Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ion
PW_C000353
Ca2+
276
16
303
8
553
14
601
2
941
15
993
21
997
35
1046
3
1163
46
1164
47
1478
49
1491
42
1552
43
2116
58
2138
17
2796
18
2937
9
3159
71
3160
72
3942
29
4186
66
4782
10
4822
28
5340
111
5780
101
7179
205
7232
211
7258
160
7281
190
11774
213
11837
198
11842
210
12198
164
12215
285
15288
151
15350
308
69336
1
77389
331
77600
115
78154
132
78266
356
78526
345
78724
130
78908
114
80413
74
80589
228
81826
51
120220
122
120465
405
121049
124
121300
418
121377
419
121850
383
121923
125
122370
409
122895
135
123099
376
123613
118
123870
454
123936
455
124403
398
124476
136
124924
137
125571
297
125711
478
125981
489
126009
299
126050
490
126533
495
127203
209
127434
506
127460
388
127502
507
128105
390
368
PIP2
Compound
6099
Compound
PW_EC000368
PIP2
80231
228
80232
168
80233
8
80234
23
290
DG
Compound
3149
Compound
PW_EC000290
DG
375
IP3
Compound
Compound
PW_EC000375
IP3
216
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
Q9NQ66
The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
HMDBP00222
PLCB1
20p12
AL050315
1
3.1.4.11
2576
14
2790
46
11646
89
69337
1
80090
308
80230
8
136124
653
136191
665
136199
66
238
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
P19174
Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.
HMDBP00244
PLCG1
20q12-q13.1
CH471077
1
3.1.4.11
4217
2
80229
8
80590
228
82835
308
88996
14
5794
Phosphoinositide 3-kinase regulatory subunit 6
Q5UE93
1
4368
8
4372
2
80282
87
1297
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
P48736
3-phosphorylates the cellular phosphoinositide PtdIns- 4,5-biphosphate (PtdIns(4,5)P2) to produce PtdIns-3, 4,5- triiphosphate (PtdIns(3,4,5)P3). Links G-protein coupled receptor activation to the secondary messenger PtdIns(3,4,5)P3 production
HMDBP01392
PIK3CG
7q22.3
CH471070
1
2.7.1.153; 2.7.11.1
4367
8
4374
2
80283
87
14445
RAC-alpha serine/threonine-protein kinase
P31749
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.
AKT1
1
2.7.11.1
80284
8
14444
Proto-oncogene vav
P15498
Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
VAV1
1
80285
8
1108
Protein kinase C alpha type
P17252
PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters
HMDBP01180
PRKCA
17q22-q23.2
X52479
1
2.7.11.13
4224
2
80281
8
136200
66
7622
akt murine thymoma viral oncogene homolog 1
1
PW_P007622
15508
14445
7621
Vav 1 guanine nucleotide exchange factor
1
PW_P007621
15507
14444
657
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
1
PW_P000657
725
216
1
305
353
1
1012
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
1
PW_P001012
1156
238
1
419
353
1
1064
Phosphatidylinositol 4,5-bisphosphate 3-kinase
1
PW_P001064
1218
5794
1
1219
1297
1
1142
Protein kinase C
1
PW_P001142
1304
1108
1
110790
PW_R110790
Right
403121
368
1
ElementCollection
false
403122
1420
1
Compound
false
403123
290
1
ElementCollection
false
403124
375
1
ElementCollection
false
101108
1012
101109
657
110794
PW_R110794
Right
403132
368
1
ElementCollection
false
403133
375
1
ElementCollection
false
101110
1064
397
Activation
PW_I000397
793
375
ElementCollection
1
794
48
Bound
1
428
Activation
PW_I000428
855
375
ElementCollection
1
856
353
Compound
1
429
Activation
PW_I000429
857
290
ElementCollection
1
858
1142
ProteinComplex
1
6
Activation
PW_I000006
11
353
Compound
1
12
1142
ProteinComplex
1
434
48
8
64521
680
482699
2164908
681
482700
2164909
1588122
1420
8
49
false
426
269
10
regular
78
78
1588123
353
8
9
false
595
398
10
regular
100
25
1588124
353
8
9
false
455
398
10
regular
100
25
1588128
353
8
51
false
733
794
10
regular
78
78
1588131
353
8
51
false
845
793
10
regular
78
78
1588613
353
8
51
false
790
609
10
regular
78
78
9588
368
37
8
false
530
198
12
regular
100
90
9589
290
37
8
false
465
598
12
regular
100
90
9590
375
37
8
false
600
598
12
regular
100
90
9593
375
37
8
false
1080
198
12
regular
100
90
594531
14445
8
2
false
1055
668
8
subunit
regular
150
70
594532
14444
8
2
false
1055
728
8
subunit
regular
150
70
594520
216
8
2
false
570
418
8
subunit
regular
150
70
594521
238
8
2
false
430
418
8
subunit
regular
150
70
594529
5794
8
2
false
780
183
8
subunit
regular
150
70
594530
1297
8
2
false
780
243
8
subunit
regular
150
70
594854
1108
8
2
false
440
798
8
subunit
regular
150
70
594856
1108
8
2
true
387
842
8
subunit
regular
150
70
482699
7622
64521
8
593198
594531
482700
7621
64521
8
593199
594532
482692
657
64521
8
593187
594520
8112
1588123
2164881
Cofactor
482693
1012
64521
8
593188
594521
8113
1588124
2164882
Cofactor
482698
1064
64521
8
593196
594529
593197
594530
482939
1142
64521
8
593494
594854
482940
1142
64521
8
593495
594856
2164880
M504 308 C560 310 581 359 580 453
5
false
18
2164881
M100 48 L100 98 L150 48 z
10
true
18
2164882
M100 153 L100 203 L150 153 z
10
true
18
2164883
M580 298 C580 329 578 415 580 453
5
false
18
false
false
true
M 712.1831854529454 292.844329429519 L 699 300 L 711.7885852216219 307.83913821981173
false
2164884
M515 598 C574 597 582 516 580 453
5
false
18
true
M 241.04113201053792 434.2855821868905 L 249 447 L 256.0315748257512 433.7502092292043
false
false
false
2164885
M650 598 C595 600 581 531 580 453
5
false
18
true
M 403.0550103927441 434.74294377040565 L 414 445 L 417.4103764592462 430.39283284116254
false
2164894
M829 687 C848 721 863 749 884 793
83
false
18
true
M 990.6360507592669 836.5068993192958 L 1003 845 L 1004.1732663260221 830.0459555260718
false
2164905
M630 248 C660 248 783 248 813 248
5
false
18
2164906
M1080 248 C1059 248 924 248 894 248
5
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
2164907
M1130 298 C1132 354 1126 566 1130 668
149
true
2
2164908
M509 884 L509 934 L559 884 z
10
true
18
2164909
M509 944 L509 994 L559 944 z
10
true
18
2164910
M1130 668 C1131 598 1131 354 1130 298
149
false
18
true
M 634.9468550441649 13.26155629629604 L 620 12 L 626.3808877211858 25.575134323078345
false
2164913
M1130 798 C1130 835 1130 908 1130 958
5
false
18
true
M 1161.6792098582403 827.5194370552929 L 1170 840 L 1176.6480894927672 826.5537028853234
false
2164914
M515 868 C514 900 803 996 1055 993
5
false
18
true
M 1080.0644009829866 873.6115180941069 L 1095 875 L 1088.7346610946918 861.3711508775821
false
2164917
M515 868 C515 934 515 1068 515 1131
5
false
18
false
false
true
M 578.0644009829867 1059.611518094107 L 593 1061 L 586.7346610946918 1047.371150877582
false
2164918
M884 871 C884 910 885 1069 885 1128
5
false
18
true
M 648.504838627043 1032.3878550430377 L 658 1044 L 663.3088318386783 1029.9708765595053
false
2164919
M681 1189 C682 1253 682 1270 682 1304
5
false
18
true
M 608.9252861840737 1241.648003085445 L 622 1249 L 621.8296591885863 1234.000967230919
false
2165879
M790 648 C760 648 730 648 700 648
149
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
2165880
M700 648 C730 648 694.5 658 724.5 658
149
true
18
2165881
M829 687 C806 730 800 744 772 794
83
false
18
true
M 890.8033488284217 831.0012891115031 L 891 846 L 903.8909390676674 838.3303396454806
false
2165882
M515 798 C515 768 465 790.5 465 760.5
149
true
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
2165883
M515 698 C515 728 515 768 515 798
149
false
18
true
M 576.5 799.5096189432334 L 584 812.5 L 591.5 799.5096189432334
false
2165886
M733 833 C697 839 622 833 590 833
149
true
18
2165887
M590 833 C628 833 695 834 733 833
149
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
488679
64521
110790
8
1958461
1588122
2164880
Left
9969
9588
2164883
Left
9970
9589
2164884
Right
9971
9590
2164885
Right
447085
101109
482692
447086
101108
482693
488687
64521
110794
8
9980
9588
2164905
Left
9981
9593
2164906
Right
447088
101110
482698
1580
397
64521
8
498
434
2164910
Right
400
9593
2164907
Left
1620
428
64521
8
663
1588613
2165879
Right
406
9590
2165880
Left
1621
429
64521
8
407
9589
2165883
Left
1656
482939
2165882
Right
1623
6
64521
8
665
1588128
2165886
Left
1657
482940
2165887
Right
57202
57770
64521
217
false
1055
958
16
regular
855
1588131
63520
2164894
63521
2164913
63522
2164914
63523
2164917
63524
2164918
63525
2164919
63550
2165881
103774
485
1273
0.2
0.2
0
9
39
2000
1055
103887
225
1010
2.2
2.2
0
2
14
327
267
159786
719
492
0.8
0.8
0
2
3
280
360
220398
M156 216 C156 166 206 116 256 116 C538 116 903 116 1185 116 C1235 116 1285 166 1285 216 C1285 628 1285 1163 1285 1575 C1285 1625 1235 1675 1185 1675 C903 1675 538 1675 256 1675 C206 1675 156 1625 156 1575 C156 1163 156 628 156 216
1
true
6
1129.0
1559.0
245329
15
Transcription Factors
485
1083
20
2.5
2.5
160
15
245375
235
Cytoplasm
205
148
20
1.2
1.2
200
15
245389
235
Endoplasmic Reticulum
735
498
20
1.3
1.3
200
15
245390
235
Nucleus
420
1494
20
1.3
1.3
200
15