64668
Pathway
Cadmium Induces DNA Synthesis and Proliferation in Macrophages
Cadmium (Cd(2+)) exposure increases the risk of cancer in humans and animals. Humans may come into contact with cadmium when smoking and ingesting contaminated food. This will increase the risk of lung cancer and prostate cancer. In the millimolar range, cadmium will inhibit cell growth. Cadmium induces DNA synthesis and proliferation and affects signal transduction and mobilization in macrophages. At micromolar concentrations, cadmium significantly increased cell division as judged by thymidine uptake and cell counts. Activating this pathway will increase the availability of the transcription factor NF(kappa)B and will activate the early genes c-fos and c-myc.
Protein
PW064798
Center
PathwayVisualizationContext65082
1915
1874
#000099
PathwayVisualization64552
64668
Cadmium Induces DNA Synthesis and Proliferation in Macrophages
Cadmium (Cd(2+)) exposure increases the risk of cancer in humans and animals. Humans may come into contact with cadmium when smoking and ingesting contaminated food. This will increase the risk of lung cancer and prostate cancer. In the millimolar range, cadmium will inhibit cell growth. Cadmium induces DNA synthesis and proliferation and affects signal transduction and mobilization in macrophages. At micromolar concentrations, cadmium significantly increased cell division as judged by thymidine uptake and cell counts. Activating this pathway will increase the availability of the transcription factor NF(kappa)B and will activate the early genes c-fos and c-myc.
Protein
1
229942
11858940
Misra UK, Gawdi G, Akabani G, Pizzo SV: Cadmium-induced DNA synthesis and cell proliferation in macrophages: the role of intracellular calcium and signal transduction mechanisms. Cell Signal. 2002 Apr;14(4):327-40.
64668
Pathway
229943
https://cgap.nci.nih.gov/Pathways/BioCarta/h_cdMacPathway
64668
Pathway
1
Cell
CL:0000000
3
Neuron
CL:0000540
2
Platelet
CL:0000233
4
Cardiomyocyte
CL:0000746
8
Beta cell
CL:0000639
6
Myocyte
CL:0000187
1
Homo sapiens
9606
Eukaryote
Human
3
Escherichia coli
562
Prokaryote
24
Solanum lycopersicum
4081
Eukaryote
Tomato
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
21
Xenopus laevis
8355
Eukaryote
African clawed frog
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
12
Mus musculus
10090
Eukaryote
Mouse
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
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
62
Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)
62977
Prokaryote
2
Bacteria
2
Prokaryote
Bacteria
5
Cytoplasm
GO:0005737
3
Mitochondrial Matrix
GO:0005759
10
Cell Membrane
GO:0005886
1
Cytosol
GO:0005829
35
Chloroplast
GO:0009507
11
Extracellular Space
GO:0005615
19
sarcoplasmic reticulum
GO:0016529
2
Mitochondrion
GO:0005739
7
Endoplasmic Reticulum Membrane
GO:0005789
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
15
Nucleus
GO:0005634
39
Mitochondrial membrane
GO:0031966
24
Brain
BTO:0000142
89
16
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
9
Muscle
BTO:0000887
141
18
11
Heart
BTO:0000562
73
10
8
5
1
1
PW_BS000008
4
3
1
1
PW_BS000004
14
10
1
PW_BS000014
2
1
1
1
PW_BS000002
73
10
1
3
PW_BS000073
85
24
10
1
1
PW_BS000085
103
3
3
1
PW_BS000103
155
3
24
1
PW_BS000155
161
3
18
1
PW_BS000161
178
3
21
1
PW_BS000178
222
3
4
1
PW_BS000024
115
10
12
PW_BS000115
211
10
18
PW_BS000024
198
5
18
1
PW_BS000024
290
5
49
1
PW_BS000024
151
1
4
1
PW_BS000151
1
1
PW_BS000001
133
3
12
1
PW_BS000133
111
5
12
1
PW_BS000111
132
1
12
1
PW_BS000132
368
3
60
1
PW_BS000028
308
10
1
1
PW_BS000024
164
4
PW_BS000164
253
5
4
1
PW_BS000024
406
3
5
1
PW_BS000115
122
5
5
1
PW_BS000122
124
1
5
1
PW_BS000124
405
10
5
PW_BS000115
120
3
17
1
PW_BS000120
135
5
17
1
PW_BS000135
118
1
17
1
PW_BS000118
376
10
17
PW_BS000053
479
3
10
1
PW_BS000115
297
5
10
1
PW_BS000024
501
3
6
1
PW_BS000115
205
5
6
1
PW_BS000024
225
35
4
1
PW_BS000024
299
1
10
1
PW_BS000024
388
1
6
1
PW_BS000112
16
2
1
2
PW_BS000016
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
49
7
1
1
PW_BS000049
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
160
1
18
1
PW_BS000160
190
11
18
PW_BS000024
213
7
18
1
PW_BS000024
210
13
18
1
PW_BS000024
285
10
4
1
PW_BS000024
331
7
12
1
PW_BS000028
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
418
24
5
1
PW_BS000115
419
25
5
1
PW_BS000115
383
7
5
1
PW_BS000100
125
13
5
1
PW_BS000125
409
11
5
PW_BS000115
454
24
17
1
PW_BS000115
455
25
17
1
PW_BS000115
398
7
17
1
PW_BS000113
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
390
7
6
1
PW_BS000112
27
15
1
PW_BS000027
231
39
1
PW_BS000024
23
15
1
1
PW_BS000023
34
5
10
1
4
PW_BS000034
45
10
1
4
PW_BS000045
52
9
10
1
6
PW_BS000052
65
11
1
PW_BS000065
651
10
62
4
PW_BS000508
654
13
62
1
PW_BS000508
89
2
PW_BS000089
653
1
62
4
PW_BS000508
665
18
1
8
PW_BS000508
936
Guanosine diphosphate
HMDB0001201
Guanosine 5'-(trihydrogen diphosphate). A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine. GDP is the product of GTP dephosphorylation by GTPases, e.g. the G-proteins that are involved in signal transduction.
146-91-8
C00035
8977
17552
GDP-4-DEHYDRO-6-DEOXY-D-MANNOSE
8630
NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1
C10H15N5O11P2
InChI=1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
QGWNDRXFNXRZMB-UUOKFMHZSA-N
[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid
443.2005
443.024329371
-2.00
7
{[(2R,3S,4R,5R)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxyphosphonic acid
0
-3
FDB022487
5'-gdp;Gdp;Guanosine 5'-(trihydrogen pyrophosphate);Guanosine 5'-diphosphate;Guanosine 5'-pyrophosphate;Guanosine mono(trihydrogen diphosphate);Guanosine pyrophosphate;Guanosine-5'-diphosphate;Guanosine-diphosphate;Ppg;Guanosine diphosphate;Guanosine 5'-diphosphoric acid
PW_C000936
GDP
83
8
238
4
1762
14
2391
2
4154
73
5007
85
5382
103
6041
155
6101
161
6488
178
7476
222
11754
115
11771
211
11823
198
12727
290
13395
151
69322
1
77142
133
77546
111
77952
132
80023
368
80080
308
80122
164
89115
253
119983
406
120068
122
121205
124
121847
405
122766
120
122820
135
123775
118
124400
376
125363
479
125445
297
126905
501
126984
205
97004
Phosphate ion
Phosphate ion, also known as orthophosphate or [PO4](3-), belongs to the class of inorganic compounds known as non-metal phosphates. These are inorganic non-metallic compounds containing a phosphate as its largest oxoanion. Inorganic salts of phosphoric acid.\n
1061
[O-]P([O-])([O-])=O
O4P
InChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-3
NBIIXXVUZAFLBC-UHFFFAOYSA-K
phosphate
94.9714
94.95342
0
phosphate
-3
-2
PW_C097003
PhosIon
80534
8
986
Guanosine triphosphate
HMDB0001273
Guanosine triphosphate (GTP) is a guanine nucleotide containing three phosphate groups esterified to the sugar moiety. GTP functions as a carrier of phosphates and pyrophosphates involved in channeling chemical energy into specific biosynthetic pathways. GTP activates the signal transducing G proteins which are involved in various cellular processes including proliferation, differentiation, and activation of several intracellular kinase cascades. Proliferation and apoptosis are regulated in part by the hydrolysis of GTP by small GTPases Ras and Rho. Another type of small GTPase, Rab, plays a role in the docking and fusion of vesicles and may also be involved in vesicle formation. In addition to its role in signal transduction, GTP also serves as an energy-rich precursor of mononucleotide units in the enzymatic biosynthesis of DNA and RNA.
86-01-1
C00044
6830
15996
GTP
6569
NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1
C10H16N5O14P3
InChI=1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
XKMLYUALXHKNFT-UUOKFMHZSA-N
({[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid
523.1804
522.990659781
-1.70
8
triphosphate, guanosine
0
-3
FDB022527
5'-gtp;Gtg;Gtp;Guanosine 5'-(tetrahydrogen triphosphate);Guanosine 5'-triphosphate;Guanosine 5'-triphosphorate;Guanosine 5'-triphosphoric acid;Guanosine triphosphate;Guanosine mono(tetrahydrogen triphosphate) (ester);H4gtp;Guanosine-5'-triphosphate
PW_C000986
GTP
81
8
240
4
1939
2
4091
14
4153
73
5006
85
5384
103
6043
155
6103
161
6490
178
7478
222
11753
115
11769
198
11981
151
12725
290
69327
1
76962
225
77144
133
77544
111
77951
132
80025
368
80088
308
80121
164
89113
253
119985
406
120066
122
121204
124
122768
120
122818
135
123774
118
125365
479
125443
297
126480
299
126907
501
126982
205
128051
388
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
1943
Cadmium
HMDB0003638
Cadmium (group IIB of the periodic table of elements) is a heavy metal. It is not a naturally occurring metal in biological systems. Cadmium poses severe risks to human health. Physiologically, it exists as an ion in the body. Up to this day, it has not been shown that cadmium has any physiological function within the human body. Interest has therefore risen in its biohazardous potential. As first described by Friedrich Stromeyer (Gottingen, Germany) in 1817, cadmium intoxication can lead to kidney, bone, and pulmonary damage. Cadmium is widely used in industrial processes, e.g as an anticorrosive agent, as a stabilizer in PVC products, as a colour pigment, a neutron absorber in nuclear power plants, and in the fabrication of nickel cadmium batteries. Phosphate fertilizers also show a big cadmium load. Although some cadmium containing products can be recycled, a large share of the general cadmium pollution is caused by dumping and incinerating cadmium polluted waste. In Scandinavia for example, cadmium concentration in agricultural soil increases by 0.2 percent per year. Total global emission of cadmium amounts to 7000 t/year. The maximum permissible value for workers according to German law is 15 ug/l. For comparison: Non-smokers show an average cadmium blood concentration of 0.5 ug/l. Basically there are three possible ways of cadmium resorption: Gastrointestinal, pulmonary and dermal. The uptake through the human gastrointestinal is approximately 5 percent of an ingested amount of cadmium, depending on the exact dose and nutritional composition. The major source of inhalative cadmium intoxication is cigarette smoke. The human lung resorbes 40 to 60 percent of the cadmium in tobacco smoke. Little research has been done on dermal absorption of cadmium. Two mechanisms facilitate cadmium absorption by the skin: binding of a free cadmium ion to sulfhydryl radicals of cysteine in epidermal keratins, or an induction and complexing with metallothionein. Once taken up by the blood, the majority of cadmium is transported bound to proteins, such as Albumin and Metallothionein. The first organ reached after cadmium uptake into the GI-blood is the liver. Here cadmium induces the production of Metallothionein. After consecutive hepatocyte necrosis and apoptosis, Cd-Metallothionein complexes are washed into sinusoidal blood. From here, parts of the absorbed cadmium enter the entero-hepatical cycle via secretion into the biliary tract in form of Cadmium-glutathione conjugates. Enzymatically degraded to cadmium-cysteine complexes in the biliary tree, cadmium reenters the small intestines. The main organ for long-term cadmium accumulation is the kidney. Here the half life period for cadmium is approximately 10 years. A life long intake can therefore lead to a cadmium accumulation in the kidney, consequently resulting in tubulus cell necrosis. The blood concentration of cadmium serves as a reliable indicator for a recent exposition, while the urinary concentration reflects past exposure, body burden and renal accumulation. Excretion of Cadmium takes place via faeces and urine. (PMID: 16961932).
22537-48-0
C01413
31193
48775
CD%2b2
28935
[Cd++]
Cd
InChI=1S/Cd/q+2
WLZRMCYVCSSEQC-UHFFFAOYSA-N
cadmium(2+) ion
112.411
113.903358121
0
cadmium(2+) ion
2
2
FDB003766
Cadmium atom;Cadmium elemental;Cadmium metallicum;Cd;Colloidal cadmium;Kadmium;Cadmium ion;Cadmium, ion (cd2+);Cd(2+);Cd2+
PW_C001943
Cd
80551
8
80556
14
344
phosphatidylinositol 4,5-bisphosphate
Compound
6073
Compound
PW_EC000344
C04637
KEGG Compound
P45B
369
Diacylglycerol
Compound
43357
Compound
PW_EC000369
Diacylg
80235
15
80236
228
346
inositol 1,4,5-trisphosphate
Compound
Compound
PW_EC000345
C01245
KEGG Compound
I145T
14389
Protein kinase C alpha type
P17252
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, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. 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 glioma cells. In intestinal 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. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells 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 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. 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
1
2.7.11.13
80261
8
80262
27
80263
231
1279
Protein kinase C beta type
P05771
Calcium-activated and phospholipid-dependent serine/threonine-protein kinase involved in various processes such as regulation of the B-cell receptor (BCR) signalosome, apoptosis and transcription regulation. Plays a key role in B-cell activation and function by regulating BCR-induced NF-kappa-B activation and B-cell suvival. Required for recruitment and activation of the IKK kinase to lipid rafts and mediates phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser- 652', leading to activate the NF-kappa-B signaling. Involved in apoptosis following oxidative damage:in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. Also involved in triglyceride homeostasis. Serves as the receptor for phorbol esters, a class of tumor promoters
HMDBP01372
PRKCB
16p11.2
FJ907246
1
2.7.11.13
69388
8
80052
164
80414
74
1808
Nuclear factor NF-kappa-B p105 subunit
P19838
NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post- translationally. p50 binds to the kappa-B consensus sequence 5'- GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105
HMDBP02145
NFKB1
4q24
BC051765
1
4145
2
4147
23
80356
8
115939
27
8561
Transcription factor p65
Q04206
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681).
RELA
1
80143
8
81923
23
5773
NF-kappa-B inhibitor alpha
P25963
NFKBIA
1
4135
2
4172
23
80142
8
1703
GTPase HRas
P01112
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
HMDBP01958
HRAS
11p15.5
BC006499
1
4092
14
4235
2
4371
8
80535
1
82723
308
89114
253
1084
RAF proto-oncogene serine/threonine-protein kinase
P04049
Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3
HMDBP01153
RAF1
3p25
M11376
1
2.7.11.1
4236
2
4544
14
11657
8
5788
Dual specificity mitogen-activated protein kinase kinase 1
Q02750
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of 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.
MAP2K1
1
2.7.12.2
4237
2
4545
14
80326
8
1117
Mitogen-activated protein kinase 1
P28482
Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity
HMDBP01190
MAPK1
22q11.2|22q11.21
Z11694
1
2.7.11.24
4038
2
11658
8
80757
23
1184
Mitogen-activated protein kinase 3
P27361
Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4)
HMDBP01263
MAPK3
16p11.2
AC012645
1
2.7.11.24
11659
8
80758
23
8784
Proto-oncogene c-Fos
P01100
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.
FOS
1
80951
23
85949
8
94903
27
1783
Transcription factor AP-1
P05412
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'
HMDBP02090
JUN
1p32-p31
BC006175
1
4109
23
4170
2
80286
8
94902
27
8433
Myc proto-oncogene protein
P01106
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.
MYC
1
43823
23
14553
CUB and zona pellucida-like domain-containing protein 1
Q86UP6
CUZD1 antiserum inhibits cell attachment and proliferation of ovarian cancer cells so may be involved in these processes. May also play a role in the uterus during late pregnancy and/or in trypsin activation in pancreatic acinar cells.
1
80549
23
1766
Tumor necrosis factor
P01375
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
HMDBP02070
TNF
6p21.3
X01394
1
4244
2
80343
228
80488
8
134406
14
1719
Voltage-dependent L-type calcium channel subunit alpha-1D
Q01668
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)
HMDBP01990
CACNA1D
3p14.3
AC132810
1
80552
8
80748
228
2719
Voltage-dependent L-type calcium channel subunit alpha-1S
Q13698
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle
HMDBP07498
CACNA1S
1q32
U30687
1
80553
8
80749
228
2715
Voltage-dependent L-type calcium channel subunit alpha-1F
O60840
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)
HMDBP07494
CACNA1F
AF196779
1
80554
8
80750
228
1845
Voltage-dependent L-type calcium channel subunit alpha-1C
Q13936
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function
HMDBP02220
CACNA1C
12p13.3
L29537
1
991
34
2767
45
3513
14
3538
52
5094
65
80555
8
80751
228
136131
651
2126
Inositol 1,4,5-trisphosphate receptor type 1
Q14643
Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate
HMDBP02849
ITPR1
3p26.1
D26070
1
967
16
2794
18
8502
10
80091
8
136138
654
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
7714
Protein kinase C complex
1
PW_P007711
15669
14389
15670
1279
80530
8
7715
NFKBIA, NFKB1, RELA complex
1
PW_P007715
15671
1808
15672
8561
15673
5773
80531
8
985
NF-kappa-B inhibitor alpha
1
PW_P000985
1111
5773
1
7716
NFKB1,RELA complex
1
PW_P007716
15674
1808
15675
8561
80532
8
7717
Nuclear factor NF-kappa-B p105 subunit with GDP and P
1
PW_P007717
15676
1808
794
936
795
97004
80533
8
954
GTPase HRas with GTP
1
PW_P000954
1080
1703
1
397
986
1
7723
RAF proto-oncogene serine/threonine-protein kinases
1
PW_P007723
15696
1084
80546
8
7724
Dual specificity mitogen-activated protein kinase kinase 1
1
PW_P007724
15697
5788
80547
8
7725
Mitogen-activated protein kinase
1
PW_P007725
15698
1117
15699
1184
80548
8
7726
Voltage-dependent L-type calcium channel
1
PW_P007726
15700
1719
15701
2719
15702
2715
15703
1845
80550
14
270
Inositol 1,4,5-trisphosphate receptor type 1
1
PW_P000270
289
2126
4
7727
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta1
1
PW_P007727
15704
216
80557
8
110904
PW_R110904
Right
403458
344
1
ElementCollection
false
403459
369
1
ElementCollection
false
403460
346
1
ElementCollection
false
470
Activation
PW_I000470
939
7714
ProteinComplex
1
940
7714
ProteinComplex
1
471
Activation
PW_I000471
941
7714
ProteinComplex
1
942
7715
ProteinComplex
1
472
Activation
PW_I000472
943
7715
ProteinComplex
1
944
985
ProteinComplex
1
473
Activation
PW_I000473
945
7715
ProteinComplex
1
946
7716
ProteinComplex
1
474
Activation
PW_I000474
947
7714
ProteinComplex
1
948
7717
ProteinComplex
1
475
Activation
PW_I000475
949
7717
ProteinComplex
1
950
954
ProteinComplex
1
481
Activation
PW_I000481
961
954
ProteinComplex
1
962
7723
ProteinComplex
1
482
Activation
PW_I000482
963
7723
ProteinComplex
1
964
7724
ProteinComplex
1
483
Activation
PW_I000483
965
7724
ProteinComplex
1
966
7725
ProteinComplex
1
486
Activation
PW_I000485
971
353
Compound
1
972
7717
ProteinComplex
1
487
Activation
PW_I000487
973
7726
ProteinComplex
1
974
1943
Compound
1
488
Activation
PW_I000488
975
1943
Compound
1
976
7726
ProteinComplex
1
489
Activation
PW_I000489
977
270
ProteinComplex
1
978
353
Compound
1
493
Activation
PW_I000493
985
369
ElementCollection
1
986
270
ProteinComplex
1
490
Activation
PW_I000490
979
7727
ProteinComplex
1
980
344
ElementCollection
1
1589340
936
8
9
false
1561
428
10
regular
100
35
1589341
97004
8
9
false
1561
408
10
regular
100
25
1589342
986
1
9
false
1491
628
10
regular
100
35
1589351
353
8
51
false
923
726
10
regular
78
78
1589356
1943
8
3
false
324
710
10
regular
100
100
1589357
1943
14
3
false
324
100
10
regular
100
100
9745
344
37
8
false
763
419
12
regular
100
90
9746
369
37
8
false
763
629
12
regular
100
90
9747
346
37
8
false
963
419
12
regular
100
90
595501
14389
8
2
false
961
596
8
subunit
regular
150
70
595502
1279
8
2
false
961
656
8
subunit
regular
150
70
595503
14389
8
2
false
1171
391
8
subunit
regular
150
70
595504
1279
8
2
false
1171
451
8
subunit
regular
150
70
595505
1808
8
2
false
1036
881
8
subunit
regular
150
70
595506
8561
8
2
false
941
916
8
subunit
regular
150
70
595507
5773
8
2
false
1031
946
8
subunit
regular
150
70
595508
5773
8
2
false
1261
776
8
subunit
regular
150
70
595509
1808
8
2
false
1036
1191
8
subunit
regular
150
70
595510
8561
8
2
false
1036
1251
8
subunit
regular
150
70
595511
1808
8
2
false
1536
453
8
subunit
regular
150
70
595512
1703
1
2
false
1466
653
8
subunit
regular
150
70
595528
1084
8
2
false
1541
800
8
subunit
regular
150
70
595533
5788
8
2
false
1471
950
8
subunit
regular
150
70
595534
1117
8
2
false
1391
1075
8
subunit
regular
150
70
595535
1184
8
2
false
1391
1135
8
subunit
regular
150
70
595536
8784
97
false
1169
1519
8
subunit
regular
150
70
595537
1783
97
false
1169
1569
8
subunit
regular
150
70
595538
8433
97
false
1174
1619
8
subunit
regular
150
70
595539
14553
97
false
1279
1539
8
subunit
regular
150
70
595540
1766
97
false
1279
1600
8
subunit
regular
150
70
595547
1719
8
76
false
299
290
8
subunit
regular
150
70
595548
2719
8
76
false
299
355
8
subunit
regular
150
70
595549
2715
8
76
false
149
290
8
subunit
regular
150
70
595550
1845
8
76
false
149
350
8
subunit
regular
150
70
595553
2126
8
8
false
743
937
8
subunit
regular
140
85
595573
216
8
2
false
513
444
8
subunit
regular
150
70
483283
7714
64552
8
594052
595501
594053
595502
483284
7714
64552
8
594054
595503
594055
595504
483285
7715
64552
8
594056
595505
594057
595506
594058
595507
483286
985
64552
8
594059
595508
483287
7716
64552
8
594060
595509
594061
595510
483288
7717
64552
8
594062
595511
8309
1589340
2167274
Cofactor
8310
1589341
2167275
Cofactor
483289
954
64552
1
594063
595512
8311
1589342
2167278
Cofactor
483294
7723
64552
8
594079
595528
483296
7724
64552
8
594084
595533
483297
7725
64552
8
594085
595534
594086
595535
483303
7726
64552
8
594093
595547
594094
595548
594095
595549
594096
595550
483306
270
64552
8
594099
595553
483318
7727
64552
8
594118
595573
2167265
M1046 696 C1076 696 1086 661 1116 661
149
true
18
2167266
M1246 521 C1247 561 1248 656 1249 692 C1210 692 1154 691 1111 691
149
false
18
true
M 443.94685504416486 1410.261556296296 L 429 1409 L 435.38088772118584 1422.5751343230784
false
2167267
M1111 691 C1141 691 1086 661 1116 661
149
true
18
2167268
M1112 879 C1111 831 1112 758 1111 691
149
false
18
true
M 443.94685504416486 1358.261556296296 L 429 1357 L 435.38088772118584 1370.5751343230784
false
false
false
2167269
M1181 981 C1211 981 1152 1125 1182 1125
149
true
18
2167270
M1336 846 C1335 890 1336 933 1336 980 C1287 981 1249 981 1181 981
149
false
18
true
M 443.94685504416486 1677.261556296296 L 429 1676 L 435.38088772118584 1689.5751343230784
false
2167271
M1181 981 C1211 981 1151 1126 1181 1126
149
true
18
2167272
M1111 1191 C1136 1190 1162 1191 1183 1191 C1182 1140 1184 1044 1181 981
149
false
18
true
M 443.94685504416486 1677.261556296296 L 429 1676 L 435.38088772118584 1689.5751343230784
false
2167273
M1321 486 C1351 486 1366 456 1396 456
149
true
18
2167274
M1556 413 L1556 463 L1606 413 z
10
true
18
2167275
M1556 393 L1556 443 L1606 393 z
10
true
18
2167276
M1536 488 C1506 488 1348 487 1318 487
149
false
18
true
M 443.94685504416486 1556.261556296296 L 429 1555 L 435.38088772118584 1568.5751343230784
false
2167277
M1686 488 C1716 488 1576 605.5 1606 605.5
149
true
18
2167278
M1561 608 L1561 658 L1611 608 z
10
true
18
2167279
M1616 688 C1616 636 1613 570 1611 523
149
false
18
true
M 443.94685504416486 1556.261556296296 L 429 1555 L 435.38088772118584 1568.5751343230784
false
2167298
M1616 688 C1646 688 1736 660.5 1766 660.5
149
true
18
2167299
M1616 800 C1617 775 1614 722 1616 688
149
false
18
true
M 451.94685504416486 1636.261556296296 L 437 1635 L 443.38088772118584 1648.5751343230784
false
2167302
M1691 835 C1721 835 1731 835 1761 835
149
true
18
2167303
M1546 950 C1585 950 1581 950 1615 950 C1615 924 1615 899 1616 870
149
false
18
true
M 451.94685504416486 1892.261556296296 L 437 1891 L 443.38088772118584 1904.5751343230784
false
2167304
M1621 985 C1651 985 1621 985 1651 985
149
true
18
2167305
M1545 1109 C1545 1076 1545 1048 1546 1020
149
false
18
true
M 451.94685504416486 1708.261556296296 L 437 1707 L 443.38088772118584 1720.5751343230784
false
2167308
M1036 1286 C1034 1323 1035 1355 1034 1395
149
false
18
true
M 674.0644009829867 2320.611518094107 L 689 2322 L 682.7346610946918 2308.3711508775823
false
2167309
M1391 1170 C1392 1214 1391 1342 1390 1395 C1333 1396 1151 1394 1072 1392
149
false
18
true
M 1689.0644009829866 2620.611518094107 L 1704 2622 L 1697.7346610946918 2608.3711508775823
false
2167310
M1186 1286 C1220 1287 1258 1287 1286 1286 C1287 1344 1287 1399 1287 1432
149
false
18
true
M 1304.0644009829866 2600.611518094107 L 1319 2602 L 1312.7346610946918 2588.3711508775823
false
2167311
M1466 1205 C1468 1269 1467 1387 1470 1465 C1454 1465 1451 1465 1432 1465
149
false
18
true
M 744.0644009829867 2430.611518094107 L 759 2432 L 752.7346610946918 2418.3711508775823
false
2167312
M1095 1477 C1131 1475 1175 1495 1186 1527
149
false
18
true
M 729.0644009829867 2706.611518094107 L 744 2708 L 737.7346610946918 2694.3711508775823
false
2167318
M1001 765 C1031 765 1449 455.5 1479 455.5
149
true
18
2167319
M1686 488 C1686 524 1684 712 1684 765 C1567 767 1085 765 1001 765
149
false
18
true
M 406.94685504416486 1496.261556296296 L 392 1495 L 398.38088772118584 1508.5751343230784
false
2167334
M324 760 C294 760 524 330 494 330
149
true
18
true
M 406.94685504416486 1439.261556296296 L 392 1438 L 398.38088772118584 1451.5751343230784
false
2167335
M374 425 C375 501 374 621 374 710
149
false
18
true
M 568.0096189432334 1558.5 L 581 1551 L 568.0096189432334 1543.5
false
2167336
M424 150 C454 150 376.5 390 406.5 390
149
true
18
2167337
M374 290 C374 261 375 229 374 200
149
false
18
true
M 406.94685504416486 1152.261556296296 L 392 1151 L 398.38088772118584 1164.5751343230784
false
2167338
M374 810 C372 892 373 976 374 1036 C463 1035 524 1037 610 1034
149
false
18
true
M 829.0644009829867 1830.611518094107 L 844 1832 L 837.7346610946918 1818.371150877582
false
2167343
M923 765 C893 765 822.5 840 792.5 840
149
true
18
true
M 406.94685504416486 1863.261556296296 L 392 1862 L 398.38088772118584 1875.5751343230784
false
2167344
M883 977 C912 978 942 978 962 978 C962 957 962 824 962 804
149
false
18
true
M 866.5096189432334 2068.5 L 879.5 2061 L 866.5096189432334 2053.5
false
2167388
M588 379 C589 400 589 417 588 444
149
false
18
true
M 680.0644009829867 1716.611518094107 L 695 1718 L 688.7346610946918 1704.371150877582
false
2167394
M863 479 C893 479 840 584 870 584
5
true
18
2167395
M813 629 C812 599 814 575 813 539
5
false
18
true
M 25.946855044164835 1413.261556296296 L 11 1412 L 17.380887721185843 1425.5751343230784
false
2167396
M963 479 C931 482 894 477 863 479
5
false
18
true
M 25.946855044164835 1413.261556296296 L 11 1412 L 17.380887721185843 1425.5751343230784
false
2167397
M813 937 C814 901 813 752 813 729
149
false
18
true
M 25.946855044164835 1435.261556296296 L 11 1434 L 17.380887721185843 1447.5751343230784
false
2167398
M863 679 C893 679 783 819 813 819
149
true
18
2167399
M663 479 C699 479 737 478 763 479
149
false
18
true
M 719.5096189432334 1767.5 L 732.5 1760 L 719.5096189432334 1752.5
false
2167400
M763 479 C733 479 695.5 464 665.5 464
149
true
18
true
M 25.946855044164835 1435.261556296296 L 11 1434 L 17.380887721185843 1447.5751343230784
false
489119
64552
110904
8
10164
9745
2167394
Left
10165
9746
2167395
Right
10166
9747
2167396
Right
1675
470
64552
8
1750
483283
2167265
Left
1751
483284
2167266
Right
1676
471
64552
8
1752
483283
2167267
Left
1753
483285
2167268
Right
1677
472
64552
8
1754
483285
2167269
Left
1755
483286
2167270
Right
1678
473
64552
8
1756
483285
2167271
Left
1757
483287
2167272
Right
1679
474
64552
8
1758
483284
2167273
Left
1759
483288
2167276
Right
1680
475
64552
1
1760
483288
2167277
Left
1761
483289
2167279
Right
1686
481
64552
8
1768
483289
2167298
Left
1769
483294
2167299
Right
1687
482
64552
8
1770
483294
2167302
Left
1771
483296
2167303
Right
1688
483
64552
8
1772
483296
2167304
Left
1773
483297
2167305
Right
1691
486
64552
8
674
1589351
2167318
Left
1777
483288
2167319
Right
1695
487
64552
8
676
1589356
2167334
Right
1779
483303
2167335
Left
1696
488
64552
14
677
1589357
2167336
Left
1780
483303
2167337
Right
1698
489
64552
8
678
1589351
2167343
Right
1781
483306
2167344
Left
1707
493
64552
419
9746
2167398
Left
1793
483306
2167397
Right
1708
490
64552
8
420
9745
2167400
Right
1794
483318
2167399
Left
63699
2167308
63700
2167309
63701
2167310
63702
2167311
63703
2167312
63705
2167338
63707
2167388
1469
595536
1470
595537
1471
595538
1472
595539
1473
595540
103805
866
1150
2.2
2.2
0
2
14
327
267
103806
514
1191
1.0
1.0
-90
2
3
280
360
220444
M125 459 C125 409 175 359 225 359 C657 359 1217 359 1649 359 C1699 359 1749 409 1749 459 C1749 832 1749 1317 1749 1690 C1749 1740 1699 1790 1649 1790 C1217 1790 657 1790 225 1790 C175 1790 125 1740 125 1690 C125 1317 125 832 125 459
1
true
6
1624.0
1431.0
245536
15
IL4 Pathway; IL10 Pathway; Cell Proliferation; Reduced Phagocytic Activity
1169
1394
20
1.6
1.6
160
15
245541
235
Extracellular
625
166
20
1.3
1.3
200
15
245542
235
Cytoplasm
165
811
20
1.3
1.3
200
15
245543
15
Putative Cadmium Binding Protein?
455
285
20
1.6
1.6
160
15
245544
15
Nucleus
898
1508
20
1.0
1.0
160
15