113072
Pathway
g-Secretase Mediated ErbB4 Signalling Pathway
The HER4/erbB4 receptor tyrosine kinase is a member of the EGF1 receptor family. HER4 is a receptor for the neuregulins (NRGs), a family of growth and differentiation factors. HER4 can also bind and be activated by heparin-binding EGF growth factor, betacellulin, and epiregulin, members of the EGF family which, unlike the NRGs, are also ligands for the EGF receptor. HER4 mRNA is expressed in several tissues such as heart, brain, kidney, and skeletal muscle, suggesting that this receptor is involved in the development and maintenance of a variety of organs and cell types. It is likely that the control of expression and function of HER4 is important in normal development as well as in disease.
Protein
PW122231
Center
PathwayVisualizationContext122507
1075
1920
#000099
PathwayVisualization112935
113072
g-Secretase Mediated ErbB4 Signalling Pathway
The HER4/erbB4 receptor tyrosine kinase is a member of the EGF1 receptor family. HER4 is a receptor for the neuregulins (NRGs), a family of growth and differentiation factors. HER4 can also bind and be activated by heparin-binding EGF growth factor, betacellulin, and epiregulin, members of the EGF family which, unlike the NRGs, are also ligands for the EGF receptor. HER4 mRNA is expressed in several tissues such as heart, brain, kidney, and skeletal muscle, suggesting that this receptor is involved in the development and maintenance of a variety of organs and cell types. It is likely that the control of expression and function of HER4 is important in normal development as well as in disease.
Protein
17
2
Platelet
CL:0000233
1
Cell
CL:0000000
4
Cardiomyocyte
CL:0000746
3
Neuron
CL:0000540
8
Beta cell
CL:0000639
5
Hepatocyte
CL:0000182
7
Epithelial Cell
CL:0000066
6
Myocyte
CL:0000187
1
Homo sapiens
9606
Eukaryote
Human
12
Mus musculus
10090
Eukaryote
Mouse
3
Escherichia coli
562
Prokaryote
6
Caenorhabditis elegans
6239
Eukaryote
Roundworm
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
5
Bos taurus
9913
Eukaryote
Cattle
17
Rattus norvegicus
10116
Eukaryote
Rat
10
Drosophila melanogaster
7227
Eukaryote
Fruit fly
24
Solanum lycopersicum
4081
Eukaryote
Tomato
21
Xenopus laevis
8355
Eukaryote
African clawed frog
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
2
Bacteria
2
Prokaryote
Bacteria
5
Cytoplasm
GO:0005737
10
Cell Membrane
GO:0005886
1
Cytosol
GO:0005829
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
3
Mitochondrial Matrix
GO:0005759
4
Peroxisome
GO:0005777
27
Peroxisome Membrane
GO:0005778
15
Nucleus
GO:0005634
26
Golgi apparatus membrane
GO:0000139
35
Chloroplast
GO:0009507
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
25
Intestine
BTO:0000648
11
Heart
BTO:0000562
73
10
9
Muscle
BTO:0000887
141
18
16
2
1
2
PW_BS000016
8
5
1
1
PW_BS000008
14
10
1
PW_BS000014
2
1
1
1
PW_BS000002
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
111
5
12
1
PW_BS000111
101
5
3
1
PW_BS000101
205
5
6
1
PW_BS000024
211
10
18
PW_BS000024
160
1
18
1
PW_BS000160
190
11
18
PW_BS000024
213
7
18
1
PW_BS000024
198
5
18
1
PW_BS000024
210
13
18
1
PW_BS000024
164
4
PW_BS000164
285
10
4
1
PW_BS000024
151
1
4
1
PW_BS000151
308
10
1
1
PW_BS000024
1
1
PW_BS000001
331
7
12
1
PW_BS000028
115
10
12
PW_BS000115
132
1
12
1
PW_BS000132
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
122
5
5
1
PW_BS000122
405
10
5
PW_BS000115
124
1
5
1
PW_BS000124
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
135
5
17
1
PW_BS000135
376
10
17
PW_BS000053
118
1
17
1
PW_BS000118
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
297
5
10
1
PW_BS000024
478
10
10
PW_BS000115
489
24
10
1
PW_BS000115
299
1
10
1
PW_BS000024
490
25
10
1
PW_BS000115
495
7
10
1
PW_BS000115
209
10
6
PW_BS000024
506
24
6
1
PW_BS000115
388
1
6
1
PW_BS000112
507
25
6
1
PW_BS000115
390
7
6
1
PW_BS000112
4
3
1
1
PW_BS000004
26
1
1
1
5
PW_BS000026
5
4
1
1
PW_BS000005
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
31
1
5
1
1
PW_BS000031
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
112
2
12
1
PW_BS000112
103
3
3
1
PW_BS000103
147
1
24
1
PW_BS000147
155
3
24
1
PW_BS000155
161
3
18
1
PW_BS000161
166
1
1
PW_BS000166
178
3
21
1
PW_BS000178
199
14
18
1
PW_BS000024
206
2
6
1
PW_BS000024
214
25
18
1
PW_BS000024
216
4
18
1
PW_BS000024
222
3
4
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
133
3
12
1
PW_BS000133
329
14
12
1
PW_BS000028
336
1
12
1
PW_BS000028
334
4
12
1
PW_BS000028
335
27
12
1
PW_BS000028
368
3
60
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
223
12
4
1
PW_BS000024
406
3
5
1
PW_BS000115
382
14
5
1
PW_BS000100
407
2
5
1
PW_BS000115
408
4
5
1
PW_BS000115
429
1
5
1
PW_BS000115
422
27
5
1
PW_BS000115
120
3
17
1
PW_BS000120
399
14
17
1
PW_BS000113
119
2
17
1
PW_BS000119
374
4
17
1
PW_BS000053
464
1
17
1
PW_BS000115
375
27
17
1
PW_BS000053
484
14
10
1
PW_BS000115
479
3
10
1
PW_BS000115
481
2
10
1
PW_BS000115
482
4
10
1
PW_BS000115
491
27
10
1
PW_BS000115
300
13
10
1
PW_BS000024
389
14
6
1
PW_BS000112
501
3
6
1
PW_BS000115
502
4
6
1
PW_BS000115
508
27
6
1
PW_BS000115
395
13
6
1
PW_BS000113
443
6
17
1
PW_BS000115
473
25
10
17
7
PW_BS000115
121
12
17
1
PW_BS000121
444
15
17
1
PW_BS000115
470
15
17
PW_BS000115
529
37
17
PW_BS000172
457
36
17
PW_BS000115
447
1
7
17
1
PW_BS000115
138
17
PW_BS000138
452
8
17
PW_BS000115
549
2
17
2
PW_BS000175
552
11
17
PW_BS000175
462
9
10
17
6
PW_BS000115
553
10
17
4
PW_BS000175
555
10
17
3
PW_BS000175
400
10
17
1
PW_BS000113
465
11
17
1
PW_BS000115
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
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
7758
Unknown
Unknown
17
3.1.1.1, 3.1.1.56
5435
118
5460
120
80644
375
80655
135
80666
376
123808
443
123811
464
124957
473
124970
121
125260
398
131937
444
131983
470
132254
119
132257
529
132260
457
132605
137
132607
447
132609
138
132610
136
132612
452
132616
549
132621
552
132622
462
132623
553
132624
555
133143
400
135385
465
21006
Receptor tyrosine-protein kinase erbB-3
Q62955
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5.
Erbb3
17
2.7.10.1
135464
135
135468
400
21084
Receptor tyrosine-protein kinase erbB-4
Q9Z2N7
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.
Erbb4
17
2.7.10.1
135243
400
135261
457
135465
135
22396
Pro-neuregulin-2, membrane-bound isoform
O35572
Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerization with the EGF receptor.
Nrg2
17
135466
135
22402
Disintegrin and metalloproteinase domain-containing protein 17
Q9Z1K9
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2 (By similarity).
Adam17
17
3.4.24.86
135467
400
21445
Presenilin-1
P97529
Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (By similarity). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity).
Psen1
17
3.4.23.-
135469
400
19606
Protein kinase C alpha type
P05696
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 (By similarity). 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
17
2.7.11.13
132032
135
133118
118
17394
Receptor tyrosine-protein kinase erbB-2
Q6P732
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (By similarity).
Erbb2
17
2.7.10.1
125076
376
12708
Receptor tyrosine-protein kinase erbB-2
17
PW_P012708
22435
7758
1
22436
21006
1
22437
21084
1
1132
353
1
1133
423
1
12709
Pro-neuregulin-2, membrane-bound isoform
17
PW_P012709
22438
22396
12710
Disintegrin and metalloproteinase domain-containing protein 17
17
PW_P012710
22439
22402
12711
Presenilin-1
17
PW_P012711
22440
21445
10608
Protein kinase C
17
PW_P010608
19068
19606
1
2805
Activation
PW_I002805
5609
12708
ProteinComplex
1
5610
12709
ProteinComplex
1
2806
Activation
PW_I002806
5611
12710
ProteinComplex
1
5612
12708
ProteinComplex
1
2807
Activation
PW_I002807
5613
12711
ProteinComplex
1
5614
12708
ProteinComplex
1
2808
Activation
PW_I002808
5615
12708
ProteinComplex
1
5616
12708
ProteinComplex
1
2809
Activation
PW_I002809
5617
12708
ProteinComplex
1
5618
10608
ProteinComplex
1
2674128
353
135
9
true
216
-206
10
regular
100
25
2674129
423
135
9
true
216
-226
10
regular
100
25
2674130
353
400
9
true
940
-243
10
regular
100
25
2674131
423
400
9
true
940
-263
10
regular
100
25
2674132
353
400
9
true
940
72
10
regular
100
25
2674133
423
400
9
true
940
52
10
regular
100
25
946146
7758
135
80
false
201
304
8
subunit
regular
200
130
946147
21006
135
2
false
186
409
8
subunit
regular
150
70
946148
21084
135
2
false
291
414
8
subunit
regular
150
70
946149
22396
135
2
false
231
127
8
subunit
regular
150
70
946150
22402
400
2
false
550
344
8
subunit
regular
150
70
946151
7758
400
80
false
945
297
8
subunit
regular
200
130
946152
21006
400
2
false
990
387
8
subunit
regular
150
70
946153
21084
400
2
false
990
447
8
subunit
regular
150
70
946154
21445
400
80
false
1485
299
8
subunit
regular
200
130
946155
7758
400
80
false
925
92
8
subunit
regular
200
130
946156
21006
400
2
false
990
722
8
subunit
regular
150
70
946157
21084
400
2
false
990
662
8
subunit
regular
150
70
946158
19606
135
2
false
550
452
8
subunit
regular
150
70
946159
21084
2
false
1290
665
8
subunit
regular
150
70
946160
17394
2
false
1300
715
8
subunit
regular
150
70
801590
12708
112935
135
942217
946146
942218
946147
942219
946148
35351
2674128
3651119
Cofactor
35352
2674129
3651120
Cofactor
801591
12709
112935
135
942220
946149
801592
12710
112935
400
942221
946150
801593
12708
112935
400
942222
946151
942223
946152
942224
946153
35353
2674130
3651124
Cofactor
35354
2674131
3651125
Cofactor
801594
12711
112935
400
942225
946154
801595
12708
112935
400
942226
946155
942227
946156
942228
946157
35355
2674132
3651130
Cofactor
35356
2674133
3651131
Cofactor
801596
10608
112935
135
942229
946158
3651119
M-504 -260 L-504 -210 L-454 -260 z
10
true
18
3651120
M-504 -280 L-504 -230 L-454 -280 z
10
true
18
3651121
M661 779.5 C661 749.5 406 -270 406 -300
149
true
18
3651122
M306 197 C306 227 306 299.5 306 329.5
149
false
18
true
M 26.946855044164835 13.26155629629604 L 12 12 L 18.380887721185843 25.575134323078345
false
true
M 768.5 304.0096189432334 L 776 317 L 783.5 304.0096189432334
false
3651123
M995 744.5 C1025 744.5 670 -155 700 -155
149
true
18
3651124
M935 -247.5 L935 -197.5 L985 -247.5 z
10
true
18
3651125
M935 -267.5 L935 -217.5 L985 -267.5 z
10
true
18
3651126
M1050 322.5 C976 326.5 626 310.5 625 344.5
149
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
false
false
3651127
M1820 734.5 C1790 734.5 1182.5 -120 1152.5 -120
149
true
18
3651128
M1050 322.5 C1086 326.5 1560 324.5 1590 324.5
149
false
18
true
M 1102.9468550441647 13.26155629629604 L 1088 12 L 1094.380887721186 25.575134323078345
false
3651129
M1050 207 C1050 223 1051 303.5 1050 322.5
149
false
18
true
M 1547.5 527.9903810567666 L 1540 515 L 1532.5 527.9903810567666
false
3651130
M935 67.5 L935 117.5 L985 67.5 z
10
true
18
3651131
M935 47.5 L935 97.5 L985 47.5 z
10
true
18
3651132
M1065 662 C1065 632 1065 542.5 1065 512.5
149
false
18
true
M 750.9468550441649 13.26155629629604 L 736 12 L 742.3808877211858 25.575134323078345
false
3651133
M1365 872.5 C1365 902.5 1130 -76.25 1130 -46.25
149
true
18
3651134
M700 487 C718 485 976 481 990 482
149
false
18
true
M 370.94685504416486 13.26155629629604 L 356 12 L 362.38088772118584 25.575134323078345
false
3651135
M625 414.5 C626 433.5 624 431 625 452
149
false
18
true
M 1033.6135115383054 545.9282204198312 L 1018.6666564941406 544.6666641235352 L 1025.0475442153265 558.2417984466135
false
3651136
M1140 697 C1176 697 1256 701 1290 700
83
false
18
true
M 1520.0644009829866 1063.611518094107 L 1535 1065 L 1528.7346610946918 1051.371150877582
false
3651137
M1438 715.5 C1455 744.5 1471 769.5 1531 765.5
147
false
20
true
M 1730.7792026654286 1493.6978222853386 L 1743 1485 L 1729.3570662760087 1478.7653901964293
false
7562
2805
112935
135
8964
801590
3651121
Left
8965
801591
3651122
Right
7563
2806
112935
400
8966
801592
3651123
Left
8967
801593
3651126
Right
7564
2807
112935
400
8968
801594
3651127
Left
8969
801593
3651128
Right
7565
2808
112935
400
8970
801593
3651129
Left
8971
801595
3651132
Right
7566
2809
112935
135
8972
801593
3651133
Left
8973
801596
3651134
Right
68109
3651135
68110
3651136
68111
3651137
3948
946159
3949
946160
185913
1232
486
1.6
1.6
0
2
14
327
267
369289
M123 471.5 C123 421.5 173 371.5 223 371.5 C678 371.5 1269 371.5 1724 371.5 C1774 371.5 1824 421.5 1824 471.5 C1824 593.5 1824 753.5 1824 875.5 C1824 925.5 1774 975.5 1724 975.5 C1269 975.5 678 975.5 223 975.5 C173 975.5 123 925.5 123 875.5 C123 753.5 123 593.5 123 471.5
1
true
6
0.0
0.0
449907
235
Cuts
712
282
20
1.0
1.0
200
15
449908
235
Cuts
1227
282
20
1.0
1.0
200
15
449909
235
Gene Transcription
1535
721
20
1.0
1.0
200
15
449910
235
Nucleus
1438
510
20
1.3
1.3
200
15
449911
235
Cytoplasm
203
835
20
1.3
1.3
200
15
449912
235
Extracellular
1423
100
19
1.3
1.3
200
15