Gene description for ERBB4
Gene name erb-b2 receptor tyrosine kinase 4
Gene symbol ERBB4
Other names/aliases ALS19
HER4
p180erbB4
Species Homo sapiens
 Database cross references - ERBB4
ExoCarta ExoCarta_2066
Vesiclepedia VP_2066
Entrez Gene 2066
HGNC 3432
MIM 600543
UniProt Q15303  
 ERBB4 identified in sEVs derived from the following tissue/cell type
Ovarian cancer cells 23333927    
Ovarian cancer cells 23333927    
Retinal pigment epithelial cells 35333565    
Retinal pigment epithelial cells 35333565    
 Gene ontology annotations for ERBB4
Molecular Function
    transcription cis-regulatory region binding GO:0000976 IMP
    protein tyrosine kinase activity GO:0004713 IDA
    transmembrane receptor protein tyrosine kinase activity GO:0004714 IBA
    transmembrane receptor protein tyrosine kinase activity GO:0004714 IDA
    GPI-linked ephrin receptor activity GO:0005004 IEA
    transmembrane-ephrin receptor activity GO:0005005 IEA
    epidermal growth factor receptor activity GO:0005006 IEA
    fibroblast growth factor receptor activity GO:0005007 IEA
    hepatocyte growth factor receptor activity GO:0005008 IEA
    insulin receptor activity GO:0005009 IEA
    insulin-like growth factor receptor activity GO:0005010 IEA
    macrophage colony-stimulating factor receptor activity GO:0005011 IEA
    platelet-derived growth factor alpha-receptor activity GO:0005018 IEA
    platelet-derived growth factor beta-receptor activity GO:0005019 IEA
    stem cell factor receptor activity GO:0005020 IEA
    vascular endothelial growth factor receptor activity GO:0005021 IEA
    epidermal growth factor receptor binding GO:0005154 IBA
    epidermal growth factor receptor binding GO:0005154 IPI
    protein binding GO:0005515 IPI
    ATP binding GO:0005524 IEA
    boss receptor activity GO:0008288 IEA
    histone H3Y41 kinase activity GO:0035401 IEA
    placental growth factor receptor activity GO:0036332 IEA
    protein tyrosine kinase collagen receptor activity GO:0038062 IEA
    neuregulin receptor activity GO:0038131 IDA
    protein homodimerization activity GO:0042803 IPI
    GABA receptor binding GO:0050811 IEA
    brain-derived neurotrophic factor receptor activity GO:0060175 IEA
    histone H2AXY142 kinase activity GO:0140801 IEA
Biological Process
    neural crest cell migration GO:0001755 ISS
    positive regulation of protein phosphorylation GO:0001934 TAS
    chromatin remodeling GO:0006338 IEA
    signal transduction GO:0007165 IDA
    cell surface receptor protein tyrosine kinase signaling pathway GO:0007169 IBA
    cell surface receptor protein tyrosine kinase signaling pathway GO:0007169 IDA
    epidermal growth factor receptor signaling pathway GO:0007173 IEA
    cell surface receptor signaling pathway via JAK-STAT GO:0007259 IEA
    multicellular organism development GO:0007275 IBA
    nervous system development GO:0007399 ISS
    synapse assembly GO:0007416 IEA
    heart development GO:0007507 ISS
    lactation GO:0007595 IMP
    positive regulation of cell population proliferation GO:0008284 IBA
    positive regulation of cell population proliferation GO:0008284 IMP
    negative regulation of cell population proliferation GO:0008285 IMP
    insulin receptor signaling pathway GO:0008286 IEA
    fibroblast growth factor receptor signaling pathway GO:0008543 IEA
    embryonic pattern specification GO:0009880 ISS
    cell migration GO:0016477 IDA
    peptidyl-tyrosine phosphorylation GO:0018108 IDA
    central nervous system morphogenesis GO:0021551 ISS
    olfactory bulb interneuron differentiation GO:0021889 ISS
    neurogenesis GO:0022008 IBA
    regulation of cell migration GO:0030334 ISS
    brain-derived neurotrophic factor receptor signaling pathway GO:0031547 IEA
    platelet-derived growth factor receptor-alpha signaling pathway GO:0035790 IEA
    platelet-derived growth factor receptor-beta signaling pathway GO:0035791 IEA
    vascular endothelial growth factor receptor-1 signaling pathway GO:0036323 IEA
    collagen-activated tyrosine kinase receptor signaling pathway GO:0038063 IEA
    vascular endothelial growth factor signaling pathway GO:0038084 IEA
    Kit signaling pathway GO:0038109 IEA
    ERBB4 signaling pathway GO:0038130 IDA
    ERBB2-ERBB4 signaling pathway GO:0038135 IEA
    ERBB4-ERBB4 signaling pathway GO:0038138 IDA
    macrophage colony-stimulating factor signaling pathway GO:0038145 IEA
    positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 IMP
    negative regulation of apoptotic process GO:0043066 IBA
    negative regulation of apoptotic process GO:0043066 IMP
    mitochondrial fragmentation involved in apoptotic process GO:0043653 IMP
    cell fate commitment GO:0045165 IEA
    positive regulation of DNA-templated transcription GO:0045893 IMP
    positive regulation of receptor signaling pathway via JAK-STAT GO:0046427 IMP
    protein autophosphorylation GO:0046777 IDA
    insulin-like growth factor receptor signaling pathway GO:0048009 IEA
    hepatocyte growth factor receptor signaling pathway GO:0048012 IEA
    ephrin receptor signaling pathway GO:0048013 IEA
    positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction GO:0051897 IEA
    positive regulation of cardiac muscle cell proliferation GO:0060045 ISS
    mammary gland epithelial cell differentiation GO:0060644 ISS
    mammary gland alveolus development GO:0060749 ISS
    cardiac muscle tissue regeneration GO:0061026 ISS
    positive regulation of ERK1 and ERK2 cascade GO:0070374 IMP
    cellular response to epidermal growth factor stimulus GO:0071364 IEA
    establishment of planar polarity involved in nephron morphogenesis GO:0072046 IEA
    neurotransmitter receptor localization to postsynaptic specialization membrane GO:0099645 IEA
    positive regulation of protein localization to cell surface GO:2000010 IEA
    negative regulation of neuron migration GO:2001223 IEA
Subcellular Localization
    extracellular region GO:0005576 TAS
    nucleus GO:0005634 IDA
    nucleoplasm GO:0005654 TAS
    mitochondrion GO:0005739 IDA
    mitochondrial matrix GO:0005759 TAS
    cytosol GO:0005829 TAS
    plasma membrane GO:0005886 IBA
    plasma membrane GO:0005886 IDA
    plasma membrane GO:0005886 TAS
    basal plasma membrane GO:0009925 IBA
    basolateral plasma membrane GO:0016323 IDA
    neuromuscular junction GO:0031594 IEA
    presynaptic membrane GO:0042734 IEA
    receptor complex GO:0043235 IBA
    receptor complex GO:0043235 IDA
    postsynaptic membrane GO:0045211 ISS
    postsynaptic density membrane GO:0098839 IEA
    glutamatergic synapse GO:0098978 IEA
    GABA-ergic synapse GO:0098982 IEA
 Experiment description of studies that identified ERBB4 in sEVs
1
Experiment ID 211
MISEV standards
✔ Biophysical techniques
✔ Enriched markers
✔ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors "Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K."
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name IGROV1
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
2
Experiment ID 212
MISEV standards
✔ Biophysical techniques
✔ Enriched markers
✔ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors "Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K."
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name OVCAR-3
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
3
Experiment ID 834
MISEV standards
✔ Biophysical techniques
✔ Enriched markers
✔ Negative markers
✔ Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35333565    
Organism Homo sapiens
Experiment description LAMP2A regulates the loading of proteins into exosomes
Authors "Ferreira JV, da Rosa Soares A, Ramalho J, Máximo Carvalho C, Cardoso MH, Pintado P, Carvalho AS, Beck HC, Matthiesen R, Zuzarte M, Girão H, van Niel G, Pereira P"
Journal name Sci Adv
Publication year 2022
Sample Retinal pigment epithelial cells
Sample name ARPE-19
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
4
Experiment ID 835
MISEV standards
✔ Biophysical techniques
✔ Enriched markers
✔ Negative markers
✔ Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35333565    
Organism Homo sapiens
Experiment description LAMP2A regulates the loading of proteins into exosomes
Authors "Ferreira JV, da Rosa Soares A, Ramalho J, Máximo Carvalho C, Cardoso MH, Pintado P, Carvalho AS, Beck HC, Matthiesen R, Zuzarte M, Girão H, van Niel G, Pereira P"
Journal name Sci Adv
Publication year 2022
Sample Retinal pigment epithelial cells
Sample name ARPE-19
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
 Protein-protein interactions for ERBB4
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 GRAP2 9402
Reconstituted Complex Homo sapiens
2 ABL2  
Protein-peptide Homo sapiens
Reconstituted Complex Homo sapiens
3 SHC1 6464
Protein-peptide Homo sapiens
Affinity Capture-MS Homo sapiens
Reconstituted Complex Homo sapiens
4 MATK  
Reconstituted Complex Homo sapiens
5 WWP1 11059
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
Biochemical Activity Homo sapiens
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
6 STAT5A 6776
Affinity Capture-Western Homo sapiens
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
7 GJA1 2697
Proximity Label-MS Homo sapiens
8 CRK 1398
Affinity Capture-MS Homo sapiens
Reconstituted Complex Homo sapiens
9 TRIM66  
Affinity Capture-MS Homo sapiens
10 BYSL 705
Reconstituted Complex Homo sapiens
Affinity Capture-Western Homo sapiens
Co-localization Homo sapiens
11 TAB1 10454
Two-hybrid Homo sapiens
12 GRB10 2887
Reconstituted Complex Homo sapiens
13 TFAP2C 7022
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
14 ANKS1A 23294
Protein-peptide Homo sapiens
15 MTMR9 66036
Two-hybrid Homo sapiens
16 SHD  
Reconstituted Complex Homo sapiens
17 GRB7 2886
Reconstituted Complex Homo sapiens
18 PTPN20B  
Two-hybrid Homo sapiens
19 NCOR1  
Affinity Capture-Western Homo sapiens
20 TRIM28 10155
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
21 PLCG2 5336
Reconstituted Complex Homo sapiens
22 HSH2D 84941
Reconstituted Complex Homo sapiens
23 PTPN12 5782
Two-hybrid Homo sapiens
24 ZAP70 7535
Reconstituted Complex Homo sapiens
25 FES 2242
Reconstituted Complex Homo sapiens
26 DUSP14 11072
Two-hybrid Homo sapiens
27 MUC1 4582
Affinity Capture-Western Homo sapiens
28 SRC 6714
Reconstituted Complex Homo sapiens
29 SYK 6850
Protein-peptide Homo sapiens
Reconstituted Complex Homo sapiens
30 MTMR2 8898
Two-hybrid Homo sapiens
31 TRO  
Reconstituted Complex Homo sapiens
Affinity Capture-Western Homo sapiens
Co-localization Homo sapiens
32 SOCS5  
Reconstituted Complex Homo sapiens
33 PTPRT  
Two-hybrid Homo sapiens
34 SHC4  
Reconstituted Complex Homo sapiens
35 PPM1A 5494
Two-hybrid Homo sapiens
36 DLG2 1740
Two-hybrid Homo sapiens
37 NUDCD1 84955
Affinity Capture-Luminescence Homo sapiens
Affinity Capture-MS Homo sapiens
38 TNS4 84951
Reconstituted Complex Homo sapiens
39 SOCS3 9021
Reconstituted Complex Homo sapiens
40 ERBB2 2064
PCA Homo sapiens
Affinity Capture-Western Homo sapiens
41 BCAR3 8412
Reconstituted Complex Homo sapiens
42 NEDD4 4734
Affinity Capture-Western Homo sapiens
Biochemical Activity Homo sapiens
Affinity Capture-Western Homo sapiens
43 YES1 7525
Reconstituted Complex Homo sapiens
44 TFAP2A  
Affinity Capture-Western Homo sapiens
45 PPM1B 5495
Two-hybrid Homo sapiens
46 XPO1 7514
Affinity Capture-Western Homo sapiens
Co-localization Homo sapiens
47 RNF41  
Reconstituted Complex Homo sapiens
48 VAV1 7409
Reconstituted Complex Homo sapiens
49 PTPRR  
Two-hybrid Homo sapiens
50 SOCS6  
Reconstituted Complex Homo sapiens
51 HCK 3055
Reconstituted Complex Homo sapiens
52 PIAS4  
Affinity Capture-Western Homo sapiens
53 LYN 4067
Reconstituted Complex Homo sapiens
54 CBL 867
Affinity Capture-Western Homo sapiens
55 TEC 7006
Reconstituted Complex Homo sapiens
56 EREG  
Affinity Capture-Luminescence Homo sapiens
57 PTK6  
Reconstituted Complex Homo sapiens
58 USP8 9101
Affinity Capture-Western Homo sapiens
59 SH2B2  
Reconstituted Complex Homo sapiens
60 SH3BP2  
Reconstituted Complex Homo sapiens
61 YAP1 10413
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
Two-hybrid Homo sapiens
Reconstituted Complex Homo sapiens
Affinity Capture-Western Homo sapiens
Two-hybrid Homo sapiens
Co-localization Homo sapiens
62 SH2D1A 4068
Reconstituted Complex Homo sapiens
63 TAB2  
Two-hybrid Homo sapiens
Affinity Capture-Western Homo sapiens
64 ITK 3702
Reconstituted Complex Homo sapiens
65 VAV2 7410
Reconstituted Complex Homo sapiens
66 ITCH 83737
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
Far Western Homo sapiens
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
Affinity Capture-Western Homo sapiens
67 SH2D2A  
Reconstituted Complex Homo sapiens
68 STAP1  
Reconstituted Complex Homo sapiens
69 TXK  
Reconstituted Complex Homo sapiens
70 PTPN11 5781
Biochemical Activity Homo sapiens
Affinity Capture-MS Homo sapiens
Two-hybrid Homo sapiens
Reconstituted Complex Homo sapiens
71 DUSP19  
Two-hybrid Homo sapiens
72 SOCS2  
Reconstituted Complex Homo sapiens
73 SLA  
Reconstituted Complex Homo sapiens
74 PTPN6 5777
Biochemical Activity Homo sapiens
Two-hybrid Homo sapiens
Reconstituted Complex Homo sapiens
75 ILKAP 80895
Two-hybrid Homo sapiens
76 SOCS1  
Reconstituted Complex Homo sapiens
77 SH2D1B  
Reconstituted Complex Homo sapiens
78 SHB 6461
Reconstituted Complex Homo sapiens
79 DLG1 1739
Affinity Capture-Western Homo sapiens
80 PTPRH 5794
Two-hybrid Homo sapiens
81 NRG2 9542
Reconstituted Complex Homo sapiens
Reconstituted Complex Homo sapiens
82 ERBB4 2066
Biochemical Activity Homo sapiens
Biochemical Activity Homo sapiens
83 EGFR 1956
Affinity Capture-Western Homo sapiens
FRET Homo sapiens
Affinity Capture-Western Homo sapiens
84 PLCG1 5335
Reconstituted Complex Homo sapiens
85 DLG4  
Co-fractionation Homo sapiens
Affinity Capture-Western Homo sapiens
Two-hybrid Homo sapiens
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
Two-hybrid Homo sapiens
Affinity Capture-Western Homo sapiens
86 PIAS3  
Affinity Capture-Western Homo sapiens
87 DUSP16  
Two-hybrid Homo sapiens
88 DUSP6 1848
Two-hybrid Homo sapiens
89 BLK 640
Reconstituted Complex Homo sapiens
90 PTPN7 5778
Two-hybrid Homo sapiens
91 CDC25C  
Two-hybrid Homo sapiens
92 LRIG1 26018
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
93 PTPDC1  
Two-hybrid Homo sapiens
94 SH2B1 25970
Reconstituted Complex Homo sapiens
95 TNS2 23371
Reconstituted Complex Homo sapiens
96 NCK1 4690
Affinity Capture-MS Homo sapiens
Reconstituted Complex Homo sapiens
97 DUSP21  
Two-hybrid Homo sapiens
98 SHC3  
Reconstituted Complex Homo sapiens
99 STYX  
Two-hybrid Homo sapiens
100 DUSP18  
Two-hybrid Homo sapiens
101 PIK3R1 5295
Reconstituted Complex Homo sapiens
102 MDM2  
Affinity Capture-Western Homo sapiens
103 PPM1F 9647
Two-hybrid Homo sapiens
104 NRG1 3084
Reconstituted Complex Homo sapiens
105 RASA1 5921
Protein-peptide Homo sapiens
Reconstituted Complex Homo sapiens
106 ANKS1B 56899
Protein-peptide Homo sapiens
107 FGR 2268
Reconstituted Complex Homo sapiens
108 SLA2 84174
Reconstituted Complex Homo sapiens
109 DUSP10 11221
Two-hybrid Homo sapiens
110 GRB2 2885
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
111 TP53 7157
Affinity Capture-Western Homo sapiens
112 DLG3 1741
Two-hybrid Homo sapiens
113 WWOX 51741
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
114 HDAC6 10013
PCA Homo sapiens
115 SH2D3C 10044
Reconstituted Complex Homo sapiens
116 SH2B3  
Reconstituted Complex Homo sapiens
117 TNS1 7145
Reconstituted Complex Homo sapiens
118 LCK 3932
Reconstituted Complex Homo sapiens
119 ABL1 25
Protein-peptide Homo sapiens
Reconstituted Complex Homo sapiens
120 INPPL1 3636
Reconstituted Complex Homo sapiens
121 HSP90AA1 3320
Affinity Capture-Luminescence Homo sapiens
122 NCK2 8440
Reconstituted Complex Homo sapiens
123 TNS3 64759
Reconstituted Complex Homo sapiens
124 LCP2 3937
Reconstituted Complex Homo sapiens
125 EPHA2 1969
Proximity Label-MS Homo sapiens
126 PIK3R2 5296
Affinity Capture-MS Homo sapiens
Reconstituted Complex Homo sapiens
127 CD44 960
Affinity Capture-Western Homo sapiens
128 SNTB2 6645
Two-hybrid Homo sapiens
129 VAV3 10451
Reconstituted Complex Homo sapiens
130 PIK3R3 8503
Reconstituted Complex Homo sapiens
131 CUL4A 8451
Affinity Capture-MS Homo sapiens
132 MTMR6 9107
Two-hybrid Homo sapiens
133 SHC2 25759
Reconstituted Complex Homo sapiens
View the network image/svg+xml
 Pathways in which ERBB4 is involved
PathwayEvidenceSource
Activation of NMDA receptors and postsynaptic events IEA Reactome
Constitutive Signaling by Aberrant PI3K in Cancer TAS Reactome
Disease TAS Reactome
Diseases of signal transduction by growth factor receptors and second messengers TAS Reactome
Downregulation of ERBB2 signaling TAS Reactome
Downregulation of ERBB4 signaling TAS Reactome
ERBB2 Activates PTK6 Signaling TAS Reactome
ERBB2 Regulates Cell Motility TAS Reactome
ESR-mediated signaling TAS Reactome
Estrogen-dependent gene expression TAS Reactome
GRB2 events in ERBB2 signaling TAS Reactome
Intracellular signaling by second messengers TAS Reactome
Long-term potentiation IEA Reactome
MAPK family signaling cascades TAS Reactome
MAPK1/MAPK3 signaling TAS Reactome
Negative regulation of the PI3K/AKT network TAS Reactome
Neuronal System IEA Reactome
Neurotransmitter receptors and postsynaptic signal transmission IEA Reactome
Nuclear signaling by ERBB4 TAS Reactome
Nuclear signaling by ERBB4 IEA Reactome
PI3K events in ERBB2 signaling TAS Reactome
PI3K events in ERBB4 signaling TAS Reactome
PI3K/AKT Signaling in Cancer TAS Reactome
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling TAS Reactome
PIP3 activates AKT signaling TAS Reactome
Post NMDA receptor activation events IEA Reactome
RAF/MAP kinase cascade TAS Reactome
SHC1 events in ERBB2 signaling IEA Reactome
SHC1 events in ERBB2 signaling TAS Reactome
SHC1 events in ERBB4 signaling TAS Reactome
Signal Transduction TAS Reactome
Signal Transduction IEA Reactome
Signaling by ERBB2 TAS Reactome
Signaling by ERBB2 IEA Reactome
Signaling by ERBB2 in Cancer TAS Reactome
Signaling by ERBB2 KD Mutants TAS Reactome
Signaling by ERBB2 TMD/JMD mutants TAS Reactome
Signaling by ERBB4 TAS Reactome
Signaling by ERBB4 IEA Reactome
Signaling by Non-Receptor Tyrosine Kinases TAS Reactome
Signaling by Nuclear Receptors TAS Reactome
Signaling by PTK6 TAS Reactome
Signaling by Receptor Tyrosine Kinases TAS Reactome
Signaling by Receptor Tyrosine Kinases IEA Reactome
Transmission across Chemical Synapses IEA Reactome





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