Summary

Name ERBB4
Full Name Receptor tyrosine-protein kinase erbB-4
Synonyms Proto-oncogene-like protein c-ErbB-4, Tyrosine kinase-type cell surface receptor HER4, p180erbB4 | HER4
Primary ID Q15303
Links - -
Type protein
Relations 45
Pathways YAP/TAZ regulation
Inhibitors N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-quinazolinyl]-2-propenamide; dacomitinib; afatinib
Function 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.

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ MAPK3down-regulates activity img/direct_inhibition.png phosphorylation ERBB4 0.532
Publications: 2 Organism: Homo Sapiens
+ CDK5up-regulates activity img/direct-activation.png phosphorylation ERBB4 0.278
Publications: 1 Organism: Homo Sapiens
+ NRG2up-regulates img/direct-activation.png binding ERBB4 0.788
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle
+ ERBB4up-regulates img/direct-activation.png binding STAT5A 0.811
Publications: 1 Organism: Homo Sapiens
+ YAP/TAZup-regulates activity img/direct-activation.png binding ERBB4 0.2
Publications: 2 Organism: Homo Sapiens
+ BTCup-regulates img/direct-activation.png binding ERBB4 0.722
Publications: 3 Organism: Homo Sapiens
Tissue: Brain
+ ERBB4up-regulates img/direct-activation.png relocalization SHC3 0.495
Publications: 2 Organism: Homo Sapiens
+ NRG3up-regulates img/direct-activation.png binding ERBB4 0.747
Publications: 3 Organism: Homo Sapiens
Tissue: Muscle
+ LRIG3up-regulates img/indirect-activation.png ERBB4 0.28
Publications: 1 Organism: Homo Sapiens
+ N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-quinazolinyl]-2-propenamidedown-regulates img/direct_inhibition.png chemical inhibition ERBB4 0.8
Publications: 1 Organism: Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding PIK3CD 0.394
Publications: 1 Organism: Homo Sapiens
+ EPGNup-regulates img/direct-activation.png binding ERBB4 0.395
Publications: 2 Organism: Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding PIK3CG 0.32
Publications: 1 Organism: Homo Sapiens
+ dacomitinibdown-regulates img/direct_inhibition.png chemical inhibition ERBB4 0.8
Publications: 2 Organism: Homo Sapiens
+ Neuregulinup-regulates img/direct-activation.png binding ERBB4 0.2
Publications: 1 Organism: Homo Sapiens
+ NRG4up-regulates img/direct-activation.png binding ERBB4 0.695
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle
+ ERBB4up-regulates img/direct-activation.png binding CBL 0.575
Publications: 2 Organism: Homo Sapiens
+ HBEGFup-regulates img/direct-activation.png binding ERBB4 0.749
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle, Smooth Muscle
+ ITCHdown-regulates quantity by destabilization img/direct_inhibition.png ubiquitination, polyubiquitination ERBB4 0.605
Publications: 2 Organism: Chlorocebus Aethiops, Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding GRB2 0.83
Publications: 2 Organism: Homo Sapiens
+ EREGup-regulates img/direct-activation.png binding ERBB4 0.705
Publications: 2 Organism: Homo Sapiens
+ ERBB2up-regulates img/direct-activation.png binding ERBB4 0.527
Publications: 1 Organism: Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding PIK3CB 0.483
Publications: 1 Organism: Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding PI3K 0.558
Publications: 1 Organism: Homo Sapiens
+ ERBB4up-regulates img/direct-activation.png binding PIK3CA 0.608
Publications: 1 Organism: Homo Sapiens
+ NRG1up-regulates img/direct-activation.png binding ERBB4 0.904
Publications: 1 Organism: Homo Sapiens
+ afatinibdown-regulates activity img/direct_inhibition.png chemical inhibition ERBB4 0.8
Publications: 1 Organism: Homo Sapiens
+ LRIG1down-regulates img/indirect_inhibition.png ERBB4 0.606
Publications: 1 Organism: Homo Sapiens
+ LRIG1down-regulates img/direct_inhibition.png ubiquitination ERBB4 0.606
Publications: 1 Organism: Homo Sapiens