112988
Pathway
Succinate Signalling During Inflammation
Succinate induces calcium mobilization in an adenylyl cyclase (AC) and protein kinase A (PKA)-dependent manner. Succinate receptor 1 (SUCNR1) engagement activates phospholipase C (PLC), resulting in the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers induce calcium mobilization and PKC activation, respectively, and subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as p38 activation. PKC-dependent phosphorylation of extracellular signal-related kinases ERK1/2 can also drive PG production. SUCNR1 signaling might act in synergy with several inflammatory signaling cascades. PKA is known to phosphorylate and activate the p65 subunit of nuclear factor κB (NF-κB) and cAMP response element-binding protein (CREB). Furthermore, NF-κB, activating protein (AP)-1, nuclear factor of activated T cells (NFAT), and ETS domain-containing protein (Elk-1) are all downstream targets of PKC and MAPKs.
Protein
PW122147
Center
PathwayVisualizationContext122423
2100
1750
#000099
PathwayVisualization112851
112988
Succinate Signalling During Inflammation
Succinate induces calcium mobilization in an adenylyl cyclase (AC) and protein kinase A (PKA)-dependent manner. Succinate receptor 1 (SUCNR1) engagement activates phospholipase C (PLC), resulting in the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers induce calcium mobilization and PKC activation, respectively, and subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as p38 activation. PKC-dependent phosphorylation of extracellular signal-related kinases ERK1/2 can also drive PG production. SUCNR1 signaling might act in synergy with several inflammatory signaling cascades. PKA is known to phosphorylate and activate the p65 subunit of nuclear factor κB (NF-κB) and cAMP response element-binding protein (CREB). Furthermore, NF-κB, activating protein (AP)-1, nuclear factor of activated T cells (NFAT), and ETS domain-containing protein (Elk-1) are all downstream targets of PKC and MAPKs.
Protein
5
1
Cell
CL:0000000
2
Platelet
CL:0000233
4
Cardiomyocyte
CL:0000746
3
Neuron
CL:0000540
8
Beta cell
CL:0000639
5
Hepatocyte
CL:0000182
6
Myocyte
CL:0000187
7
Epithelial Cell
CL:0000066
1
Homo sapiens
9606
Eukaryote
Human
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
12
Mus musculus
10090
Eukaryote
Mouse
5
Bos taurus
9913
Eukaryote
Cattle
17
Rattus norvegicus
10116
Eukaryote
Rat
10
Drosophila melanogaster
7227
Eukaryote
Fruit fly
6
Caenorhabditis elegans
6239
Eukaryote
Roundworm
3
Escherichia coli
562
Prokaryote
24
Solanum lycopersicum
4081
Eukaryote
Tomato
21
Xenopus laevis
8355
Eukaryote
African clawed frog
23
Pseudomonas aeruginosa
287
Prokaryote
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
2
Bacteria
2
Prokaryote
Bacteria
19
Schizosaccharomyces pombe
4896
Eukaryote
5
Cytoplasm
GO:0005737
1
Cytosol
GO:0005829
7
Endoplasmic Reticulum Membrane
GO:0005789
10
Cell Membrane
GO:0005886
11
Extracellular Space
GO:0005615
19
sarcoplasmic reticulum
GO:0016529
2
Mitochondrion
GO:0005739
24
Mitochondrial Intermembrane Space
GO:0005758
25
Golgi apparatus
GO:0005794
14
Mitochondrial Outer Membrane
GO:0005741
12
Mitochondrial Inner Membrane
GO:0005743
13
Endoplasmic Reticulum
GO:0005783
6
Lysosome
GO:0005764
16
Lysosomal Lumen
GO:0043202
36
Membrane
GO:0016020
3
Mitochondrial Matrix
GO:0005759
4
Peroxisome
GO:0005777
31
Periplasmic Space
GO:0005620
27
Peroxisome Membrane
GO:0005778
15
Nucleus
GO:0005634
26
Golgi apparatus membrane
GO:0000139
35
Chloroplast
GO:0009507
20
Endoplasmic Reticulum Lumen
GO:0005788
8
Smooth Endoplasmic Reticulum
GO:0005790
34
Plant-Type Vacuole
GO:0000325
39
Mitochondrial membrane
GO:0031966
37
Basolateral cell membrane
GO:0016323
2
Endothelium
BTO:0000393
5
cardiocyte
BTO:0001539
1
Liver
BTO:0000759
72
9
18
Pancreas
BTO:0000988
8
Blood Vessel
BTO:0001102
74
11
7
Nervous System
BTO:0001484
11
Heart
BTO:0000562
73
10
9
Muscle
BTO:0000887
141
18
25
Intestine
BTO:0000648
8
5
1
1
PW_BS000008
2
1
1
1
PW_BS000002
160
1
18
1
PW_BS000160
198
5
18
1
PW_BS000024
151
1
4
1
PW_BS000151
111
5
12
1
PW_BS000111
132
1
12
1
PW_BS000132
122
5
5
1
PW_BS000122
124
1
5
1
PW_BS000124
135
5
17
1
PW_BS000135
118
1
17
1
PW_BS000118
297
5
10
1
PW_BS000024
299
1
10
1
PW_BS000024
205
5
6
1
PW_BS000024
388
1
6
1
PW_BS000112
49
7
1
1
PW_BS000049
331
7
12
1
PW_BS000028
383
7
5
1
PW_BS000100
390
7
6
1
PW_BS000112
398
7
17
1
PW_BS000113
16
2
1
2
PW_BS000016
14
10
1
PW_BS000014
15
11
1
PW_BS000015
21
5
1
1
4
PW_BS000021
35
5
19
1
4
PW_BS000035
3
2
1
1
PW_BS000003
46
1
1
4
PW_BS000046
47
19
1
4
PW_BS000047
42
24
1
1
PW_BS000042
43
25
1
1
PW_BS000043
58
1
14
1
1
PW_BS000058
17
12
1
1
PW_BS000017
18
13
1
1
PW_BS000018
9
6
1
1
PW_BS000009
71
11
1
3
PW_BS000071
72
5
1
3
PW_BS000072
29
1
1
1
PW_BS000029
66
18
5
1
8
PW_BS000066
10
1
7
1
1
PW_BS000010
28
1
16
1
1
PW_BS000028
101
5
3
1
PW_BS000101
211
10
18
PW_BS000024
190
11
18
PW_BS000024
213
7
18
1
PW_BS000024
210
13
18
1
PW_BS000024
164
4
PW_BS000164
285
10
4
1
PW_BS000024
308
10
1
1
PW_BS000024
1
1
PW_BS000001
115
10
12
PW_BS000115
356
25
12
1
PW_BS000028
345
24
12
1
PW_BS000028
130
13
12
1
PW_BS000130
114
11
12
PW_BS000114
74
1
3
PW_BS000074
228
36
1
PW_BS000024
51
8
1
PW_BS000051
405
10
5
PW_BS000115
418
24
5
1
PW_BS000115
419
25
5
1
PW_BS000115
125
13
5
1
PW_BS000125
409
11
5
PW_BS000115
376
10
17
PW_BS000053
454
24
17
1
PW_BS000115
455
25
17
1
PW_BS000115
136
13
17
1
PW_BS000136
137
11
17
PW_BS000137
478
10
10
PW_BS000115
489
24
10
1
PW_BS000115
490
25
10
1
PW_BS000115
495
7
10
1
PW_BS000115
209
10
6
PW_BS000024
506
24
6
1
PW_BS000115
507
25
6
1
PW_BS000115
4
3
1
1
PW_BS000004
31
1
5
1
1
PW_BS000031
5
4
1
1
PW_BS000005
103
3
3
1
PW_BS000103
155
3
24
1
PW_BS000155
161
3
18
1
PW_BS000161
107
31
3
PW_BS000107
108
1
3
PW_BS000108
178
3
21
1
PW_BS000178
117
1
3
1
PW_BS000117
166
1
1
PW_BS000166
163
2
18
1
PW_BS000163
219
31
4
PW_BS000024
220
1
4
PW_BS000024
222
3
4
1
PW_BS000024
223
12
4
1
PW_BS000024
318
31
23
PW_BS000024
315
1
23
PW_BS000024
322
1
23
1
PW_BS000024
133
3
12
1
PW_BS000133
134
12
12
1
PW_BS000134
112
2
12
1
PW_BS000112
129
1
5
12
1
PW_BS000129
334
4
12
1
PW_BS000028
368
3
60
1
PW_BS000028
119
2
17
1
PW_BS000119
406
3
5
1
PW_BS000115
407
2
5
1
PW_BS000115
414
1
5
5
1
PW_BS000115
408
4
5
1
PW_BS000115
384
12
5
1
PW_BS000100
120
3
17
1
PW_BS000120
450
1
5
17
1
PW_BS000115
374
4
17
1
PW_BS000053
121
12
17
1
PW_BS000121
479
3
10
1
PW_BS000115
481
2
10
1
PW_BS000115
482
4
10
1
PW_BS000115
480
12
10
1
PW_BS000115
501
3
6
1
PW_BS000115
206
2
6
1
PW_BS000024
502
4
6
1
PW_BS000115
391
12
6
1
PW_BS000112
26
1
1
1
5
PW_BS000026
22
14
1
1
PW_BS000022
39
7
1
1
3
PW_BS000039
59
27
1
1
PW_BS000059
23
15
1
1
PW_BS000023
7
1
1
PW_BS000007
91
8
5
1
1
PW_BS000091
54
1
3
1
5
PW_BS000054
56
26
1
1
PW_BS000056
104
14
3
1
PW_BS000104
147
1
24
1
PW_BS000147
199
14
18
1
PW_BS000024
214
25
18
1
PW_BS000024
216
4
18
1
PW_BS000024
225
35
4
1
PW_BS000024
249
13
4
1
PW_BS000024
288
14
4
1
PW_BS000024
226
4
4
1
PW_BS000024
290
5
49
1
PW_BS000024
329
14
12
1
PW_BS000028
336
1
12
1
PW_BS000028
335
27
12
1
PW_BS000028
184
1
2
1
PW_BS000024
372
10
2
PW_BS000028
253
5
4
1
PW_BS000024
27
15
1
PW_BS000027
382
14
5
1
PW_BS000100
429
1
5
1
PW_BS000115
422
27
5
1
PW_BS000115
399
14
17
1
PW_BS000113
464
1
17
1
PW_BS000115
375
27
17
1
PW_BS000053
484
14
10
1
PW_BS000115
491
27
10
1
PW_BS000115
300
13
10
1
PW_BS000024
389
14
6
1
PW_BS000112
508
27
6
1
PW_BS000115
395
13
6
1
PW_BS000113
36
1
20
1
1
PW_BS000036
11
1
8
1
1
PW_BS000011
95
1
7
2
1
PW_BS000095
123
1
7
5
1
PW_BS000123
141
1
7
19
1
PW_BS000141
78
8
1
1
PW_BS000078
298
1
7
10
1
PW_BS000024
293
4
1
PW_BS000024
332
1
7
12
1
PW_BS000028
447
1
7
17
1
PW_BS000115
13
1
2
1
PW_BS000013
6
1
3
1
PW_BS000006
102
12
3
1
PW_BS000102
126
6
5
1
PW_BS000126
127
1
16
5
1
PW_BS000127
156
12
24
1
PW_BS000156
162
12
18
1
PW_BS000162
179
12
21
1
PW_BS000179
224
2
4
1
PW_BS000024
215
6
18
1
PW_BS000024
227
34
4
1
PW_BS000024
291
6
49
1
PW_BS000024
292
4
49
1
PW_BS000024
301
6
10
1
PW_BS000024
302
1
16
10
1
PW_BS000024
113
6
12
1
PW_BS000113
337
1
16
12
1
PW_BS000028
358
39
12
PW_BS000028
369
12
60
1
PW_BS000028
443
6
17
1
PW_BS000115
448
1
16
17
1
PW_BS000115
207
6
6
1
PW_BS000024
182
5
PW_BS000024
385
10
5
1
PW_BS000100
569
1
5
4
PW_BS000314
410
15
5
1
PW_BS000115
435
15
5
PW_BS000115
526
37
5
PW_BS000172
421
36
5
PW_BS000115
416
8
5
PW_BS000115
542
2
5
2
PW_BS000174
545
11
5
PW_BS000174
427
9
10
5
6
PW_BS000115
546
10
5
4
PW_BS000174
548
10
5
3
PW_BS000174
438
25
10
5
7
PW_BS000115
430
11
5
1
PW_BS000115
6123
PIP2(18:1(11Z)/20:3(8Z,11Z,14Z))
HMDB0010082
PIP2(18:1(11Z)/20:3(8Z,11Z,14Z)) is a phosphatidylinositol bisphosphate. Phosphatidylinositol bisphosphates are acidic (anionic) phospholipids that consist of a phosphatidic acid backbone, linked via the phosphate group to a bisphosphorylated inositol (hexahydroxycyclohexane). Phosphatidylinositol bisphosphates are generated from phosphatidylinositols which are phosphorylated by a number of different kinases that place the phosphate moiety on positions 4 and 5 of the inositol ring, although position 3 can also be phosphorylated. Phosphatidylinositols bisphosphates can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 18 and 20 carbons are the most common. PIP2(18:1(11Z)/20:3(8Z,11Z,14Z)), in particular, consists of one chain of vaccenic acid at the C-1 position and one chain of homo-g-linolenic acid at the C-2 position. The vaccenic acid moiety is derived from butter fat and animal fat, while the homo-g-linolenic acid moiety is derived from fish oils, liver and kidney. The most important phosphatidylinositol bisphosphate in both quantitative and biological terms is phosphatidylinositol 4,5-bisphosphate. Phosphatidylinositol and the phosphatidylinositol phosphates are the main source of diacylglycerols that serve as signaling molecules, via the action of phospholipase C enzymes. Phosphatidylinositols phosphates are usually present at low levels only in tissues, typically at about 1 to 3% of the concentration of phosphatidylinositol.
C00626
53480273
Phosphatidylinositols
24767959
CCCCCC\C=C/CCCCCCCCCC(=O)OC[C@]([H])(COP(O)(=O)O[C@H]1C(O)C(O)C(OP(=O)(O)O)[C@@H](OP(=O)(O)O)C1O)OC(=O)CCCCCC\C=C/C\C=C/C\C=C/CCCCC
C47H85O19P3
InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13-14,16-17,19,22,24,39,42-47,50-52H,3-10,12,15,18,20-21,23,25-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/b13-11-,16-14-,19-17-,24-22-/t39-,42?,43?,44?,45+,46?,47+/m1/s1
QMRUSFNQFVPOME-RZEZUQAISA-N
{[(4S,6S)-2,3,5-trihydroxy-4-({hydroxy[(2R)-2-[(8Z,11Z,14Z)-icosa-8,11,14-trienoyloxy]-3-[(11Z)-octadec-11-enoyloxy]propoxy]phosphoryl}oxy)-6-(phosphonooxy)cyclohexyl]oxy}phosphonic acid
1047.0877
1046.489790074
-4.60
8
[(4S,6S)-2,3,5-trihydroxy-4-{[hydroxy(2R)-2-[(8Z,11Z,14Z)-icosa-8,11,14-trienoyloxy]-3-[(11Z)-octadec-11-enoyloxy]propoxyphosphoryl]oxy}-6-(phosphonooxy)cyclohexyl]oxyphosphonic acid
0
-5
C00626
1-(11z-octadecenoyl)-2-(8z,11z,14z-eicosatrienoyl)-sn-glycero-3-phospho-(1'-myo-inositol-3',4'-bisphosphate);1-phosphatidyl-d-myo-inositol 4,5-bisphosphate;1-phosphatidyl-delta-myo-inositol 4,5-bisphosphate;1-vaccenoyl-2-homo-g-linolenoyl-sn-glycero-3-phosphoinositol-bisphosphate;1-vaccenoyl-2-homo-gamma-linolenoyl-sn-glycero-3-phosphoinositol-bisphosphate;Pip2(18:1/20:3);Pip2(18:1n7/20:3n6);Pip2(18:1w7/20:3w6);Pip2(38:4);Pip2[3',4'](18:1(11z)/20:3(8z,11z,14z));Phosphatidylinositol diphosphate(18:1/20:3);Phosphatidylinositol diphosphate(18:1n7/20:3n6);Phosphatidylinositol diphosphate(18:1w7/20:3w6);Phosphatidylinositol diphosphate(38:4)
PW_C006123
PIP211
113030
8
892
Inositol 1,3,4-trisphosphate
HMDB0001143
Inositol 1,3,4-trisphosphate, also known as 1,3,4-itp or I3S, belongs to the class of organic compounds known as inositol phosphates. Inositol phosphates are compounds containing a phosphate group attached to an inositol (or cyclohexanehexol) moiety. Inositol 1,3,4-trisphosphate is soluble (in water) and an extremely strong acidic compound (based on its pKa). Within the cell, inositol 1,3,4-trisphosphate is primarily located in the cytoplasm. In humans, inositol 1,3,4-trisphosphate is involved in the inositol metabolism pathway and the inositol phosphate metabolism pathway. Inositol 1,3,4-trisphosphate is a specific regulator of cellular signaling.
98102-63-7
C01243
439455
18228
INOSITOL-1-3-4-TRIPHOSPHATE
388561
DB01729
O[C@@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@@H](O)[C@H]1OP(O)(O)=O
C6H15O15P3
InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2-,3+,4+,5+,6+/m1/s1
MMWCIQZXVOZEGG-MLQGYMEPSA-N
{[(1S,2R,3R,4S,5S,6S)-2,3,5-trihydroxy-4,6-bis(phosphonooxy)cyclohexyl]oxy}phosphonic acid
420.0956
419.962379346
-1.45
9
inositol 1,3,4-trisphosphate
0
-6
FDB022450
1,3,4-itp;1d-myo-inositol 1,3,4-trisphosphate;D-myo-inositol 1,3,4-trisphosphate;I3s;Inositol 1,3,4-triphosphate;Inositol 1,3,4-trisphosphate;Myo-inositol 1,3,4-trisphosphate;D-myo-inositol 1,3,4-trisphosphoric acid;Inositol 1,3,4-trisphosphoric acid
PW_C000892
InoTrip
2056
8
2440
2
7385
160
7419
198
12223
151
78185
111
78210
132
121998
122
122441
124
124551
135
125008
118
126147
297
126592
299
127754
205
128164
388
3163
DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0)
HMDB0007112
DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0) is a diglyceride, or a diacylglycerol (DAG). It is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Diacylglycerols can have many different combinations of fatty acids attached at both the C-1 and C-2 positions. DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0), in particular, consists of one chain of palmitic acid at the C-1 position and one chain of arachidonic acid at the C-2 position. The palmitic acid moiety is derived from fish oils, milk fats, vegetable oils and animal fats, while the arachidonic acid moiety is derived from animal fats and eggs. Mono- and diacylglycerols are common food additives used to blend together certain ingredients, such as oil and water, which would not otherwise blend well. Dacylglycerols are often found in bakery products, beverages, ice cream, chewing gum, shortening, whipped toppings, margarine, and confections. Synthesis of diacylglycerol begins with glycerol-3-phosphate, which is derived primarily from dihydroxyacetone phosphate, a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells). Glycerol-3-phosphate is first acylated with acyl-coenzyme A (acyl-CoA) to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. Phosphatidic acid is then de-phosphorylated to form diacylglycerol.Diacylglycerols are precursors to triacylglycerols (triglyceride), which are formed by the addition of a third fatty acid to the diacylglycerol under the catalysis of diglyceride acyltransferase. Since diacylglycerols are synthesized via phosphatidic acid, they will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position.
C00165
9543736
77096
DIACYLGLYCEROL
7822686
[H][C@](CO)(COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
C39H68O5
InChI=1S/C39H68O5/c1-3-5-7-9-11-13-15-17-18-19-20-22-24-26-28-30-32-34-39(42)44-37(35-40)36-43-38(41)33-31-29-27-25-23-21-16-14-12-10-8-6-4-2/h11,13,17-18,20,22,26,28,37,40H,3-10,12,14-16,19,21,23-25,27,29-36H2,1-2H3/b13-11-,18-17-,22-20-,28-26-/t37-/m0/s1
YJEMDFYSDGNQNM-NDUZERMISA-N
(2S)-1-(hexadecanoyloxy)-3-hydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
616.9542
616.506675286
-7.58
1
diacylglycerol
0
0
FDB024306
1-palmitoyl-2-arachidonoyl-sn-glycerol;Dag(16:0/20:4);Dag(16:0/20:4n6);Dag(16:0/20:4w6);Dag(36:4);Dg(16:0/20:4);Dg(16:0/20:4n6);Dg(16:0/20:4w6);Dg(36:4);Diacylglycerol;Diacylglycerol(16:0/20:4);Diacylglycerol(16:0/20:4n6);Diacylglycerol(16:0/20:4w6);Diacylglycerol(36:4);Diglyceride;(2s)-1-hydroxy-3-(palmitoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate;1,2-dg 16:0/20:4(omega-6);1-hexadecanoyl-2-(5z,8z,11z,14z)-eicosatetraenoyl-sn-glycerol;1-hexadecanoyl-2-(5z,8z,11z,14z)-icosatetraenoyl-sn-glycerol;1-hexadecanoyl-2-(5z,8z,11z,14z-eicosatetraenoyl)-sn-glycerol;Dag(16:0/20:4omega6);Dg(16:0/20:4(5z,8z,11z,14z)/0:0);Dg(16:0/20:4/0:0);Dg(16:0/20:4omega6);Diacylglycerol(16:0/20:4omega6);(2s)-1-hydroxy-3-(palmitoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoic acid
PW_C003163
DG36:4
16217
49
83621
331
97420
383
113465
8
114710
390
116929
398
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
174
Succinic acid
HMDB0000254
Succinic acid is a dicarboxylic acid. The anion, succinate, is a component of the citric acid cycle capable of donating electrons to the electron transfer chain. Succinate dehydrogenase (SDH) plays an important role in the mitochondria, being both part of the respiratory chain and the Krebs cycle. SDH with a covalently attached FAD prosthetic group, binds enzyme substrates (succinate and fumarate) and physiological regulators (oxaloacetate and ATP). Oxidizing succinate links SDH to the fast-cycling Krebs cycle portion where it participates in the breakdown of acetyl-CoA throughout the whole Krebs cycle. The succinate can readily be imported into the mitochondrial matrix by the n-butylmalonate- (or phenylsuccinate-) sensitive dicarboxylate carrier in exchange with inorganic phosphate or another organic acid, e. g. malate. (PMID 16143825) Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase are associated with a wide spectrum of clinical presentations (i.e.: Huntington's disease. (PMID 11803021).
110-15-6
C00042
1110
15741
SUC
1078
DB00139
OC(=O)CCC(O)=O
C4H6O4
InChI=1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8)
KDYFGRWQOYBRFD-UHFFFAOYSA-N
butanedioic acid
118.088
118.02660868
0.25
2
succinic acid
0
-2
FDB001931
1,2-ethanedicarboxylate;1,2-ethanedicarboxylic acid;1,4-butanedioate;1,4-butanedioic acid;Amber acid;Asuccin;Dihydrofumarate;Dihydrofumaric acid;Katasuccin;Succinate;Wormwood acid;Acide butanedioique;Acide succinique;Acidum succinicum;Bernsteinsaeure;Butandisaeure;Butanedionic acid;E363;Ethylenesuccinic acid;Hooc-ch2-ch2-cooh;Spirit of amber;Butanedionate;Ethylenesuccinate
PW_C000174
Succini
152
3
239
4
502
18
507
8
676
31
1265
5
4255
17
5383
103
6042
155
6102
161
6454
107
6455
108
6489
178
6764
117
6836
166
7362
163
7455
219
7456
220
7477
222
11866
198
12142
151
13259
223
42368
318
42369
315
42402
322
77143
133
77213
134
77483
111
77738
112
77749
129
78426
334
80024
368
80721
119
112846
308
113428
1
119984
406
120192
407
120385
122
120555
414
120990
408
122565
384
122767
120
123029
135
123189
450
123555
374
125138
121
125364
479
125549
481
125930
482
126713
480
126906
501
127082
206
127389
502
128304
391
423
Magnesium
HMDB0000547
Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.
22537-22-0
C00305
888
18420
13-HYDROXY-MAGNESIUM-PROTOPORP
865
DB01378
[Mg++]
Mg
InChI=1S/Mg/q+2
JLVVSXFLKOJNIY-UHFFFAOYSA-N
magnesium(2+) ion
24.305
23.985041898
0
magnesium(2+) ion
2
2
FDB003518
Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+
PW_C000423
Mg2+
86
8
227
4
268
16
476
2
727
26
811
5
819
18
883
22
936
39
983
3
992
21
1167
46
1483
49
1529
43
1764
14
2124
10
2411
59
2942
23
3126
29
3373
7
4540
31
4774
91
4869
54
4974
56
5253
104
5329
111
5356
112
5376
103
5906
147
5934
151
6038
155
6094
161
6250
166
6484
178
6594
164
6881
160
6979
199
7170
205
7194
206
7227
213
7233
211
7250
214
7310
216
7313
198
7473
222
11763
132
11843
210
12312
225
12324
249
12513
288
12581
226
12729
290
15275
285
15337
308
77137
133
77236
329
77937
336
78393
334
78417
335
78489
115
78522
331
78536
356
78574
130
80020
368
80045
184
80048
372
80623
118
80654
135
80865
15
80965
253
81841
51
93832
383
94900
27
108596
223
110559
390
115687
398
119974
406
120070
122
120247
382
120702
407
120981
408
121181
124
121265
429
121319
419
121924
125
122086
405
122408
422
122759
120
122921
399
123307
119
123546
374
123835
464
123889
455
124477
136
124637
376
124978
375
125447
297
125598
484
125669
479
125777
481
125921
482
125947
299
125973
495
126000
490
126243
478
126553
491
126753
300
127125
389
127164
501
127380
502
127407
388
127451
507
127804
209
128125
508
128347
395
1799
Heme
HMDB0003178
Heme is the color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins.
14875-96-8
C00032
17627
HEME_A
24604415
DB02577
CC1=C(CCC(O)=O)C2=CC3=[N+]4C(=CC5=C(C)C(C=C)=C6C=C7C(C)=C(C=C)C8=[N+]7[Fe--]4(N2C1=C8)N56)C(C)=C3CCC(O)=O
C34H32FeN4O4
InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
KABFMIBPWCXCRK-RGGAHWMASA-L
4,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide
616.487
616.177297665
-5.48
2
4,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide
0
-2
FDB016272
(protoporphyrinato)iron;Ferroheme;Ferroheme b;Ferroprotoheme;Ferroprotoporphyrin;Ferroprotoporphyrin ix;Ferrous protoheme;Ferrous protoheme ix;Haem;Hem;Heme;Iron protoporphyrin;Iron protoporphyrin ix;Iron(ii) protoporphyrin ix;Protoferroheme;Protohaem;Protoheme;Protoheme ix;Reduced hematin
PW_C001799
Heme
247
16
308
10
324
8
608
2
766
5
1244
3
1354
49
1413
36
1963
18
2806
29
2938
9
3238
11
3367
26
3421
14
3734
4
4043
31
4823
28
5170
95
5472
123
5485
125
5517
129
5830
141
6246
78
6283
1
6597
151
7044
160
7060
161
7326
213
11835
198
11898
211
12065
164
13009
298
13021
300
42278
17
76915
293
76931
249
77351
111
77364
130
77367
331
77398
332
77517
115
77629
336
77813
334
78380
133
78602
132
78963
112
79932
134
120431
405
120603
408
120955
407
121085
383
121658
429
121746
124
121910
122
122570
406
122691
384
123065
376
123133
447
123144
136
123228
374
123521
119
123650
398
124216
464
124297
118
124463
135
125142
120
125277
121
125742
482
125896
481
126196
299
126499
297
126512
495
126718
479
126827
480
127224
502
127357
206
127632
388
128070
205
128083
395
128086
390
128309
501
128434
391
964
FAD
HMDB0001248
FAD, also known as flavitan or adeflavin, belongs to the class of organic compounds known as flavin nucleotides. These are nucleotides containing a flavin moiety. Flavin is a compound that contains the tricyclic isoalloxazine ring system, which bears 2 oxo groups at the 2- and 4-positions. FAD is a drug which is used to treat eye diseases caused by vitamin b2 deficiency, such as keratitis and blepharitis. FAD is slightly soluble (in water) and a moderately acidic compound (based on its pKa). FAD has been found in human liver and muscle tissues, and has also been detected in multiple biofluids, such as feces and blood. Within the cell, FAD is primarily located in the cytoplasm, mitochondria, endoplasmic reticulum and peroxisome. FAD exists in all living organisms, ranging from bacteria to humans. In humans, FAD is involved in the risedronate action pathway, the ibandronate action pathway, the valine, leucine and isoleucine degradation pathway, and the pyrimidine metabolism pathway. FAD is also involved in several metabolic disorders, some of which include the oncogenic action OF L-2-hydroxyglutarate in hydroxygluaricaciduria pathway, gaba-transaminase deficiency, 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, and the saccharopinuria/hyperlysinemia II pathway. FAD is a condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972).
146-14-5
C00016
643975
16238
FAD
559059
DB03147
CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)CO[P@](O)(=O)O[P@@](O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC3=C1N=CN=C3N)C1=NC(=O)NC(=O)C1=N2
C27H33N9O15P2
InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1
VWWQXMAJTJZDQX-UYBVJOGSSA-N
{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}[({[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}(hydroxy)phosphoryl)oxy]phosphinic acid
785.5497
785.157134455
-2.27
9
flavine-adenine dinucleotide
0
-3
FDB022511
1h-purin-6-amine flavin dinucleotide;1h-purin-6-amine flavine dinucleotide;Adenine-flavin dinucleotide;Adenine-flavine dinucleotide;Adenine-riboflavin dinuceotide;Adenine-riboflavin dinucleotide;Adenine-riboflavine dinucleotide;Fad;Flamitajin b;Flanin f;Flavin adenine dinucleotide;Flavin adenine dinucleotide oxidized;Flavin-adenine dinucleotide;Flavine adenosine diphosphate;Flavine-adenine dinucleotide;Flavitan;Flaziren;Isoalloxazine-adenine dinucleotide;Riboflavin 5'-adenosine diphosphate;Riboflavin-adenine dinucleotide;Riboflavine-adenine dinucleotide;Adeflavin
PW_C000964
FAD
99
9
114
5
186
8
192
3
216
4
253
17
628
28
825
18
840
2
1188
14
1489
42
1612
29
1622
49
2133
58
2536
22
3723
26
4602
36
4688
31
4741
13
4758
10
4881
6
5268
103
5285
102
5335
111
5496
126
5511
127
5613
118
6030
155
6054
156
6082
161
6116
162
6390
1
6475
178
6499
179
6666
107
7039
163
7175
205
7321
213
7465
222
7487
223
9076
224
11818
216
11887
215
11899
211
12296
225
12328
249
12443
151
12519
227
12595
226
12710
291
12720
292
13029
301
13041
302
43623
318
77080
293
77126
133
77152
134
77501
113
77507
112
77518
115
77541
334
77615
132
77726
337
78054
329
78375
345
78930
331
79222
336
79272
358
80012
368
80034
369
80714
119
119958
406
119999
384
120051
408
120107
407
120432
405
120453
122
120490
124
121278
429
121298
418
121417
382
121489
383
122748
120
122776
121
122802
374
122823
443
123066
376
123087
135
123166
448
123849
464
123868
454
123976
399
124047
398
125348
479
125378
480
125429
482
125474
481
125697
297
125979
489
126107
299
126277
484
126891
501
126920
391
126968
502
126987
207
127011
206
127310
209
127432
506
127602
388
127840
389
1170
Flavin Mononucleotide
HMDB0001520
Flavin mononucleotide (FMN), or riboflavin-5?-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, the reversible interconversion of oxidized (FMN), semiquinone (FMNH) and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. Flavin mononucleotide is also used as an orange-red food colour additive. It is the principal form in which riboflavin is found in cells and tissues.
146-17-8
C00061
643976
17621
FMN
559060
DB03247
CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)COP(O)(O)=O)C1=NC(=O)NC(=O)C1=N2
C17H21N4O9P
InChI=1S/C17H21N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,22-24H,5-6H2,1-2H3,(H,20,25,26)(H2,27,28,29)/t11-,12+,14-/m0/s1
FVTCRASFADXXNN-SCRDCRAPSA-N
{[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}phosphonic acid
456.3438
456.104614802
-2.83
6
riboflavin 5'-phosphate
0
-3
FDB001984
Fmn;Flanin;Flavine mononucleotide;Flavol;Riboflavin;Riboflavin 5'-monophosphate;Riboflavin 5'-phosphate;Riboflavin mononucleotide;Riboflavin monophosphate;Riboflavin phosphate;Riboflavin-5'-phosphate na;Riboflavin-5-phosphate;Riboflavine 5'-monophosphate;Riboflavine 5'-phosphate;Riboflavine dihydrogen phosphate;Riboflavine monophosphate;Riboflavine phosphate;Riboflavine-5'-phosphate;Vitamin b2 phosphate;Flavin mononucleotide;Riboflavin 5'-(dihydrogen phosphate)
PW_C001170
FlvnMnt
539
8
1190
14
1692
2
4961
31
5772
101
11900
211
12313
225
77519
115
77590
111
78730
132
120433
405
120454
122
121929
124
123067
376
123088
135
124482
118
125698
297
126104
299
127190
205
127312
209
127686
388
19
Tetrahydrobiopterin
HMDB0000027
Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. In fact it is used by all three human nitric-oxide synthases (NOS) eNOS, nNOS, and iNOS as well as the enzyme glyceryl-ether monooxygenase. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. Specifically, tetrahydrobiopterin is a cofactor for tryptophan 5-hydroxylase 1, tyrosine 3-monooxygenase, and phenylalanine hydroxylase all of which are essential for the formation of the neurotransmitters dopamine, noradrenaline and adrenaline. Tetrahydrobiopterin has been proposed to be involved in promotion of neurotransmitter release in the brain and the regulation of human melanogenesis. A defect in BH4 production and/or a defect in the enzyme dihydropteridine reductase (DHPR) causes phenylketonuria type IV, as well as dopa-responsive dystonias. BH4 is also implicated in Parkinson's disease, Alzheimer's disease and depression. Tetrahydrobiopterin is present in probably every cell or tissue of higher animals. On the other hand, most bacteria, fungi and plants do not synthesize tetrahydrobiopterin. -- Wikipedia.
17528-72-2
C00272
1125
15372
TETRA-H-BIOPTERIN
1093
DB00360
CC(O)C(O)C1CNC2=C(N1)C(=O)N=C(N)N2
C9H15N5O3
InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)
FNKQXYHWGSIFBK-UHFFFAOYSA-N
2-amino-6-(1,2-dihydroxypropyl)-1,4,5,6,7,8-hexahydropteridin-4-one
241.2471
241.117489371
-2.04
6
tetrahydrobiopterin
0
0
FDB021880
(1r,2s)-(2-amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1h)-pteridinone;5,6,7,8-erythro-tetrahydrobiopterin;5,6,7,8-tetra-h-biopterin;5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;5,6,7,8-tetrahydrobiopterin;L-erythro-2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3h)-pteridinon;Tetra-h-biopterin;Tetra-hydro-biopterin;Tetrahydrobiopterin;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-pteridinone;Bh4
PW_C000019
BH4
1957
2
4085
8
4800
14
4803
14
4962
31
11901
211
77520
115
78663
132
120434
405
121616
124
123068
376
124174
118
126493
299
127585
388
1867
Nitric oxide
HMDB0003378
The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function. The use of nitrates is well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide (PMID: 16966108, 8752507, 17181668, 16005189). Nitric oxide is used as a food additive (EAFUS: Everything Added to Food in the United States).
10102-43-9
C00533
145068
16480
NITRIC-OXIDE
127983
DB00435
[N]=O
NO
InChI=1S/NO/c1-2
MWUXSHHQAYIFBG-UHFFFAOYSA-N
nitroso
30.0061
29.997988627
0
nitric oxide
0
0
FDB021825
Mononitrogen monoxide;Nitric oxide;Nitrogen monoxide;Nitrogen oxide;Nitrogen protoxide;Nitrosyl hydride;Nitrosyl radical;Nitroxide radical;Nitroxyl;(no)(.);[no];Edrf;Endothelium-derived relaxing factor;Monoxido de nitrogeno;Monoxyde d'azote;Nitrogen monooxide;Nitrosyl;No;(.)no;No(.);Oxido de nitrogeno(ii);Oxido nitrico;Oxyde azotique;Oxyde nitrique;Stickstoff(ii)-oxid;Stickstoffmonoxid
PW_C001867
NO
4795
14
4799
14
11896
211
77514
115
80331
8
120428
405
123062
376
949
Prostaglandin E2
HMDB0001220
The naturally occurring prostaglandin E2 (PGE2) is known in medicine as dinoprostone, and it is the most common and most biologically active of the mammalian prostaglandins. It has important effects during labour and also stimulates osteoblasts to release factors which stimulate bone resorption by osteoclasts (a type of bone cell that removes bone tissue by removing the bone's mineralized matrix). PGE2 is also the prostaglandin that ultimately induces fever. PGE2 has been shown to increase vasodilation and cAMP production, enhance the effects of bradykinin and histamine, and induce uterine contractions and platelet aggregation. PGE2 is also responsible for maintaining the open passageway of the fetal ductus arteriosus, decreasing T-cell proliferation and lymphocyte migration, and activating the secretion of IL-1α and IL-2. PGE2 exhibits both pro- and anti-inflammatory effects, particularly on dendritic cells (DC). Depending on the nature of maturation signals, PGE2 has different and sometimes opposite effects on DC biology. PGE2 exerts an inhibitory action, reducing the maturation of DC and their ability to present antigen. PGE2 has also been shown to stimulate DC and promote IL-12 production when given in combination with TNF-alpha. PGE2 is an environmentally bioactive substance. Its action is prolonged and sustained by other factors especially IL-10. It modulates the activities of professional DC by acting on their differentiation, maturation, and their ability to secrete cytokines. PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC). PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype (PMID: 16978535). Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and are able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signalling pathways.
363-24-6
C00584
5280360
15551
5Z13E-15S-1115-DIHYDROXY-9-OXOPROS
4444059
DB00917
CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O
C20H32O5
InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1
XEYBRNLFEZDVAW-ARSRFYASSA-N
(5Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]hept-5-enoic acid
352.4651
352.224974134
-3.90
3
dinoprostone
0
-1
FDB022498
(-)-prostaglandin e2;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(5z,13e,15s)-11-alpha,15-dihydroxy-9-oxoprost-5,13-dienoate;(5z,13e,15s)-11-alpha,15-dihydroxy-9-oxoprost-5,13-dienoic acid;5-trans-pge2;Dinoprostone;Dinoprostonum;Glandin;L-prostaglandin e2;Minprositin e2;Minprostin e2;Pge2;Prepidil;Prostaglandin e;Prostaglandin e2;Prostaglandin e2alpha;Prostarmon e;Prostin;Prostin e2;(15s)-prostaglandin e2;(5z,11alpha,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(e,z)-(1r,2r,3r)-7-(3-hydroxy-2-((3s)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid;(z)-7-((1r,2r,3r)-3-hydroxy-2-((s,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid;Dinoproston;Dinoprostona;Propess;(5z,11a,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11a,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(5z,11alpha,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11α,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11α,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(e,z)-(1r,2r,3r)-7-(3-hydroxy-2-((3s)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoate;(z)-7-((1r,2r,3r)-3-hydroxy-2-((s,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoate
PW_C000949
PGE2
613
2
1361
49
77423
331
115883
8
121092
383
123657
398
17406
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
P10894
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.
PLCB1
5
3.1.4.11
122512
405
131853
182
131867
122
133002
385
134117
569
19514
NF-kappa-B inhibitor zeta
A7Z059
Involved in regulation of NF-kappa-B transcription factor complexes. Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation. Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer. Seems also to activate NF-kappa-B-mediated transcription. In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters. Promotes transcription of LCN2 and DEFB4. Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS. Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling. May promote apoptosis (By similarity). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (By similarity).
NFKBIZ
5
131862
410
131923
122
131924
435
132955
124
19509
Inhibitor of nuclear factor kappa-B kinase subunit beta
Q95KV0
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.
IKBKB
5
2.7.11.10
131900
122
132954
405
19503
Inhibitor of nuclear factor kappa-B kinase subunit alpha
A7YWD1
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor.
CHUK
5
2.7.11.10
131899
122
132953
405
20023
NF-kappa-B essential modulator
Q5EA16
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).
IKBKG
5
131901
122
7764
Unknown
Unknown
5
3.1.1.1, 3.1.1.56
5473
123
5486
125
120135
122
120349
406
120525
124
121238
126
121241
429
122400
384
122507
405
131832
410
131877
435
132247
407
132250
526
132253
421
132587
409
132590
182
132592
416
132594
542
132599
545
132600
427
132601
546
132602
548
133000
385
133575
438
133591
383
135142
430
19458
Mitogen-activated protein kinase 13
Q3T0N5
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells (By similarity).
MAPK13
5
2.7.11.24
131898
122
132946
124
135039
410
135178
435
15333
Nitric oxide synthase, endothelial
P29473
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
NOS3
5
1.14.13.39
120435
405
131925
122
19608
Protein kinase C alpha type
P04409
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation. In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
PRKCA
5
2.7.11.13
131926
122
132981
124
19413
Mitogen-activated protein kinase 1
A2VE60
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint (By similarity). Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2.
MAPK1
5
2.7.11.24
132939
124
133038
122
135012
410
16075
Prostaglandin G/H synthase 1
A7YWD4
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (By similarity).
PTGS1
5
1.14.99.1
121118
383
131927
122
132589
125
19379
Cyclic AMP-responsive element-binding protein 1
O18957
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-117 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
CREB1
5
131833
410
131928
435
132919
124
10519
Phospholipase C, beta 1
5
PW_P010519
18953
17406
1
10527
Nuclear factor NF-kappa-B p105 subunit
5
PW_P010527
18962
19514
1
10572
Inhibitor of nuclear factor kappa-B kinase subunit beta
5
PW_P010572
19025
19509
1
10573
Inhibitor of nuclear factor kappa-B kinase
5
PW_P010573
19026
19503
19027
19509
19028
20023
10574
Succinate receptor 1
5
PW_P010574
19029
7764
10575
Mitogen-activated protein kinase 11
5
PW_P010575
19030
19458
1
10536
Nitric-oxide synthase, endothelial
5
PW_P010536
18971
15333
2
10521
Protein kinase C
5
PW_P010521
18955
19608
1
12053
ERK1, ERK2
5
PW_P012053
21406
19413
10576
COX1 homodimer complex
5
PW_P010576
19031
16075
1
10495
Cyclic AMP-responsive element-binding protein 1
5
PW_P010495
18924
19379
1
165427
PW_R165427
Right
621430
6123
1
Compound
false
621431
892
1
Compound
false
621432
3163
1
Compound
false
155719
10519
3.1.4.11
165428
PW_R165428
Right
621433
10527
1
ProteinComplex
false
621434
10572
1
ProteinComplex
false
621435
10527
1
ProteinComplex
false
155720
10573
9389
PW_T009389
9660
10527
1
ProteinComplex
122
435
Unknown
1151
Activation
PW_I001151
2301
10574
ProteinComplex
1
2302
10519
ProteinComplex
1
1311
Activation
PW_I001311
2621
174
Compound
1
2622
10574
ProteinComplex
1
974
Activation
PW_I000974
1947
892
Compound
1
1948
353
Compound
1
1312
Activation
PW_I001312
2623
353
Compound
1
2624
10575
ProteinComplex
1
1313
Activation
PW_I001313
2625
353
Compound
1
2626
10536
ProteinComplex
1
1155
Activation
PW_I001155
2309
10536
ProteinComplex
1
2310
1867
Compound
1
1156
Activation
PW_I001156
2311
3163
Compound
1
2312
10521
ProteinComplex
1
1695
Activation
PW_I001695
3389
10521
ProteinComplex
1
3390
12053
ProteinComplex
1
1696
Activation
PW_I001696
3391
12053
ProteinComplex
1
3392
10576
ProteinComplex
1
1157
Activation
PW_I001157
2313
10576
ProteinComplex
1
2314
949
Compound
1
1158
Activation
PW_I001158
2315
10521
ProteinComplex
1
2316
10573
ProteinComplex
1
1159
Activation
PW_I001159
2317
10575
ProteinComplex
1
2318
10495
ProteinComplex
1
2673442
6123
122
3
false
247
604
10
regular
100
100
2673443
892
122
3
false
877
594
10
regular
100
120
2673444
3163
122
3
false
877
789
10
regular
100
100
2673445
353
122
9
true
547
476
10
regular
100
25
2673446
174
385
3
false
572
76
10
regular
100
100
2673447
353
122
51
false
1168
614
10
regular
78
78
2673448
423
122
9
false
1426
600
10
regular
100
25
2673449
1799
122
9
true
977
717
10
regular
100
25
2673450
964
122
9
true
977
697
10
regular
100
25
2673451
1170
122
9
true
977
667
10
regular
100
35
2673452
19
122
9
true
977
647
10
regular
100
25
2673453
1867
122
64
false
1168
347
10
regular
78
78
2673454
949
122
3
false
877
1244
10
regular
100
110
943452
17406
122
2
false
567
621
8
subunit
regular
150
70
943453
19514
122
2
false
277
789
8
subunit
regular
150
70
943454
19509
122
2
false
447
789
8
subunit
regular
150
70
943455
19514
122
2
false
362
1149
8
subunit
regular
150
70
943456
19503
122
2
false
222
969
8
subunit
regular
150
70
943457
19509
122
2
false
362
969
8
subunit
regular
150
70
943458
20023
122
2
false
502
969
8
subunit
regular
150
70
943459
19514
435
2
false
367
1584
8
subunit
regular
150
70
943460
7764
122
80
false
517
216
8
subunit
regular
200
130
943461
19458
122
2
false
1401
615
8
subunit
regular
150
70
943462
15333
122
2
false
1132
487
8
subunit
regular
150
70
943463
19608
122
2
false
852
969
8
subunit
regular
150
70
943464
19413
122
2
false
712
1104
8
subunit
regular
150
70
943465
19413
122
2
false
852
1104
8
subunit
regular
150
70
943466
16075
122
2
false
1132
1104
8
subunit
regular
150
70
943468
19379
435
2
false
401
1725
8
subunit
regular
150
70
799882
10519
112851
122
939602
943452
35035
2673445
3646688
Cofactor
799883
10527
112851
122
939603
943453
799884
10572
112851
122
939604
943454
799885
10527
112851
122
939605
943455
799886
10573
112851
122
939606
943456
939607
943457
939608
943458
799887
10527
112851
435
939609
943459
799888
10574
112851
122
939610
943460
799889
10575
112851
122
939611
943461
35036
2673448
3646701
Cofactor
799890
10536
112851
122
939612
943462
35037
2673449
3646704
Cofactor
35038
2673450
3646705
Cofactor
35039
2673451
3646706
Cofactor
35040
2673452
3646707
Cofactor
799891
10521
112851
122
939613
943463
799892
12053
112851
122
939614
943464
939615
943465
799893
10576
112851
122
939616
943466
799895
10495
112851
435
939618
943468
3646685
M347 654 C377 654 537 656 567 656
5
false
18
3646686
M877 654 C847 654 747 656 717 656
5
false
18
true
M 758.9468550441649 456.92821279043665 L 744 455.6666564941406 L 750.3808877211858 469.24179081721894
false
3646687
M877 839 C847 839 673 838 643 838 C642 802 642 791 642 691
5
false
18
true
M 758.9468550441649 456.92821279043665 L 744 455.6666564941406 L 750.3808877211858 469.24179081721894
false
3646688
M-53 486 L-53 536 L-3 486 z
10
true
18
3646689
M352 859 C392 911 397 921 437 969
5
false
18
3646690
M522 859 C488 907 478 918 437 969
5
false
18
3646691
M437 1149 C437 1119 437 1069 437 1039
5
false
18
true
M 1005.6135420558836 887.5948692845773 L 990.6666870117188 886.3333129882812 L 997.0475747329045 899.9084473113596
false
3646692
M437 1219 C437 1249 442 1554 442 1584
83
false
18
true
M 1410.5 1440.0096189432334 L 1418 1453 L 1425.5 1440.0096189432334
false
3646693
M442 1584 C442 1554 437 1229 437 1199
83
true
18
true
M 1490.5 1970.0096189432334 L 1498 1983 L 1505.5 1970.0096189432334
false
3646694
M642 331 C642 361 642 591 642 621
149
false
18
true
M 1570.5 645.7596189432334 L 1578 658.75 L 1585.5 645.7596189432334
false
3646695
M642 621 C642 591 597 434.75 597 404.75
149
true
18
true
M 596.2801680324461 210.26155629629605 L 581.3333129882812 209 L 587.714200709467 222.57513432307834
false
3646696
M622 176 C622 206 622 211 622 241
149
false
18
true
M 1545.5 374.5096189432334 L 1553 387.5 L 1560.5 374.5096189432334
false
3646697
M622 241 C622 211 572 163.5 572 133.5
149
true
18
true
M 596.2801680324461 210.26155629629605 L 581.3333129882812 209 L 587.714200709467 222.57513432307834
false
3646698
M977 654 C1000 655 1142 655 1168 653
149
false
18
true
M 1961.6231060406117 720.4742253874945 L 1974 712 L 1960.4726585573405 705.5184081049707
false
3646699
M1207 614 C1207 584 802 613.5 802 583.5
149
true
18
true
M 1022.9468550441649 210.26155629629605 L 1008 209 L 1014.3808877211858 222.57513432307834
false
3646700
M1246 653 C1276 653 1371 650 1401 650
149
false
18
true
M 2132.0096189432334 719.5 L 2145 712 L 2132.0096189432334 704.5
false
3646701
M1286 610 L1286 660 L1336 610 z
10
true
18
3646702
M1221 465.5 C1191 465.5 1194 458 1164 458
149
true
18
true
M 960.2801680324461 210.26155629629605 L 945.3333129882812 209 L 951.714200709467 222.57513432307834
false
3646703
M1207 614 C1207 596 1206 577 1207 557
149
false
18
true
M 2005.5 834.7596189432334 L 2013 847.75 L 2020.5 834.7596189432334
false
3646704
M972 712 L972 762 L1022 712 z
10
true
18
3646705
M972 692 L972 742 L1022 692 z
10
true
18
3646706
M972 662 L972 712 L1022 662 z
10
true
18
3646707
M972 642 L972 692 L1022 642 z
10
true
18
3646708
M1032 732 C1032 702 1032 623.75 1032 593.75
149
true
18
true
M 1036.2802290676022 518.261556296296 L 1021.3333740234375 517 L 1027.7142617446234 530.5751343230784
false
3646709
M1207 425 C1207 437 1207 473 1207 487
149
false
18
true
M 1285.6134810207272 627.5948692845773 L 1270.6666259765625 626.3333129882812 L 1277.0475136977484 639.9084473113596
false
3646710
M1052 572 C1052 602 1027 827.75 1027 857.75
149
true
18
3646711
M927 889 C927 919 927 939 927 969
149
false
18
true
M 1770.5 942.5096189432334 L 1778 955.5 L 1785.5 942.5096189432334
false
3646712
M927 969 C927 939 797 731.5 797 701.5
149
true
18
true
M 1285.6134810207272 627.5948692845773 L 1270.6666259765625 626.3333129882812 L 1277.0475136977484 639.9084473113596
false
3646713
M927 1039 C927 1069 927 1074 927 1104
149
false
18
true
M 1770.5 1170.0096189432334 L 1778 1183 L 1785.5 1170.0096189432334
false
3646714
M927 1104 C927 1074 797 959 797 929
149
true
18
true
M 830.9468550441649 718.261556296296 L 816 717 L 822.3808877211858 730.5751343230784
false
3646715
M1002 1139 C1017 1139 1117 1139 1132 1139
149
false
18
true
M 1770.5 1390.0096189432334 L 1778 1403 L 1785.5 1390.0096189432334
false
3646716
M1207 1104 C1207 1074 797 1179 797 1149
149
true
18
true
M 830.9468550441649 846.261556296296 L 816 845 L 822.3808877211858 858.5751343230784
false
3646719
M927 1244 C927 1214 927 1204 927 1174
149
false
18
true
M 1181.6134810207272 947.5948692845773 L 1166.6666259765625 946.3333129882812 L 1173.0475136977484 959.9084473113596
false
3646720
M1207 1174 C1207 1204 957 1579 957 1609
149
true
18
3646721
M852 1004 C838 1004 672 1005 652 1004
149
false
18
true
M 1625.5 1150.0096189432334 L 1633 1163 L 1640.5 1150.0096189432334
false
3646722
M577 969 C577 939 792 1014 792 984
149
true
18
true
M 1058.9468550441647 658.261556296296 L 1044 657 L 1050.380887721186 670.5751343230784
false
3646723
M1476 685 C1476 715 1482 1736 1482 1766 C1449 1765 588 1758 551 1760
149
false
18
true
M 2314.5 1012.2596189432334 L 2322 1025.25 L 2329.5 1012.2596189432334
false
3646724
M476 1725 C476 1695 1341 801.25 1341 771.25
149
true
18
true
M 932.9468550441649 674.261556296296 L 918 673 L 924.3808877211858 686.5751343230784
false
3646725
M1207 692 C1208 711 1207 1085 1207 1104
149
false
18
true
M 1923.0644009829866 1476.611518094107 L 1938 1478 L 1931.7346610946918 1464.371150877582
false
3646726
M442 1654 C458 1679 639.5 1615 684.5 1599
147
false
18
true
M 1570.5644009829866 2263.611518094107 L 1585.5 2265 L 1579.2346610946918 2251.3711508775823
false
3646727
M476 1725 C485 1684 549.5 1640 675.5 1600
147
false
18
false
false
795732
112851
165427
122
3217761
2673442
3646685
Left
3217762
2673443
3646686
Right
3217763
2673444
3646687
Right
751863
155719
799882
795733
112851
165428
122
18134
799883
3646689
Left
18135
799884
3646690
Left
18136
799885
3646691
Right
751864
155720
799886
77673
9389
112851
663
799885
3646692
Left
664
799887
3646693
Right
6315
1151
112851
122
7064
799888
3646694
Left
7065
799882
3646695
Right
6316
1311
112851
385
1582
2673446
3646696
Left
7066
799888
3646697
Right
6317
974
112851
122
1583
2673443
3646698
Left
1584
2673447
3646699
Right
6318
1312
112851
122
1585
2673447
3646700
Left
7067
799889
3646702
Right
6319
1313
112851
122
1586
2673447
3646703
Left
7068
799890
3646708
Right
6320
1155
112851
122
1587
2673453
3646709
Right
7069
799890
3646710
Left
6321
1156
112851
122
1588
2673444
3646711
Left
7070
799891
3646712
Right
6322
1695
112851
122
7071
799891
3646713
Left
7072
799892
3646714
Right
6323
1696
112851
122
7073
799892
3646715
Left
7074
799893
3646716
Right
6324
1157
112851
122
1589
2673454
3646719
Right
7075
799893
3646720
Left
6325
1158
112851
122
7076
799891
3646721
Left
7077
799886
3646722
Right
6326
1159
112851
435
7078
799889
3646723
Left
7079
799895
3646724
Right
67781
3646725
67782
3646726
67783
3646727
185759
261
1312
2.2
2.2
0
2
14
327
267
369211
M126 392 C126 342 176 292 226 292 C620 292 1131 292 1525 292 C1575 292 1625 342 1625 392 C1625 843 1625 1428 1625 1879 C1625 1929 1575 1979 1525 1979 C1131 1979 620 1979 226 1979 C176 1979 126 1929 126 1879 C126 1428 126 843 126 392
1
true
6
1499.0
1687.0
449443
235
DNA Transcription
716
1549
20
1.0
1.0
200
15
449444
235
Nucleus
511
1334
20
1.6
1.6
200
15
449445
235
Cytoplasm
183
328
20
1.6
1.6
200
15
449446
235
Extracellular
1273
153
20
1.6
1.6
200
15