ERBB4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AHX, 2L2T, 2LCX, 2R4B, 3BBT, 3BBW, 3BCE, 3U2P, 3U7U, 3U9U
Identifiers
Aliases	ERBB4, ALS19, HER4, p180erbB4, erb-b2 receptor tyrosine kinase 4
External IDs	OMIM: 600543 MGI: 104771 HomoloGene: 21084 GeneCards: ERBB4
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q34 Start 211,375,717 bp[1] End 212,538,841 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C3|1 33.8 cM Start 68,071,345 bp[2] End 69,147,218 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell secondary oocyte optic nerve middle temporal gyrus Brodmann area 23 entorhinal cortex Brodmann area 46 orbitofrontal cortex right uterine tube corpus callosum Top expressed in superior frontal gyrus interventricular septum visual cortex corneal stroma plantaris muscle extensor digitorum longus muscle cingulate gyrus sciatic nerve aortic valve hand More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity protein homodimerization activity epidermal growth factor receptor binding kinase activity protein binding transmembrane receptor protein tyrosine kinase activity ATP binding protein tyrosine kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity receptor tyrosine kinase transmembrane signaling receptor activity Cellular component integral component of membrane cytosol membrane receptor complex plasma membrane nucleoplasm extracellular region mitochondrial matrix basolateral plasma membrane mitochondrion nucleus postsynaptic membrane glutamatergic synapse GABA-ergic synapse integral component of presynaptic membrane integral component of postsynaptic density membrane cytoplasm integral component of plasma membrane basal plasma membrane Biological process mitochondrial fragmentation involved in apoptotic process negative regulation of neuron migration cell fate commitment positive regulation of protein phosphorylation regulation of cell migration regulation of transcription, DNA-templated olfactory bulb interneuron differentiation embryonic pattern specification phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway central nervous system morphogenesis mammary gland alveolus development transcription, DNA-templated nervous system development mammary gland epithelial cell differentiation MAPK cascade positive regulation of phosphatidylinositol 3-kinase activity positive regulation of transcription, DNA-templated multicellular organism development heart development protein phosphorylation positive regulation of cardiac muscle cell proliferation neural crest cell migration positive regulation of ERK1 and ERK2 cascade positive regulation of protein localization to cell surface protein autophosphorylation cardiac muscle tissue regeneration positive regulation of phosphatidylinositol 3-kinase signaling peptidyl-tyrosine phosphorylation lactation cell population proliferation cell migration signal transduction negative regulation of cell population proliferation apoptotic process ERBB2 signaling pathway phosphatidylinositol phosphate biosynthetic process peptidyl-tyrosine autophosphorylation positive regulation of cell population proliferation positive regulation of apoptotic process regulation of cell motility negative regulation of apoptotic process cellular response to epidermal growth factor stimulus positive regulation of tyrosine phosphorylation of STAT protein positive regulation of protein kinase B signaling positive regulation of receptor signaling pathway via JAK-STAT synapse assembly negative regulation of signal transduction cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2066 13869 Ensembl ENSG00000178568 ENSMUSG00000062209 UniProt Q15303 Q61527 RefSeq (mRNA) NM_001042599 NM_005235 NM_010154 RefSeq (protein) NP_001036064 NP_005226 NP_034284 Location (UCSC) Chr 2: 211.38 – 212.54 Mb Chr 1: 68.07 – 69.15 Mb PubMed search [3] [4]
Wikidata
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Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene.^[5][6] Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.^[7]

Function

Receptor tyrosine-protein kinase erbB-4 is a receptor tyrosine kinase that is a member of the epidermal growth factor receptor family. ERBB4 is a single-pass type I transmembrane protein with multiple furin-like cysteine rich domains, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins-2, -3 and -4, heparin-binding EGF-like growth factor and betacellulin. Ligand binding induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment.^[7]

Clinical significance

Mutations in this gene have been associated with cancer.^[7] Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia.^[8] Single-nucleotide polymorphisms in ERBB4 have also been found in a study of patients with familial amyotrophic lateral sclerosis type 19.^[9]

Interactions

ERBB4 has been shown to interact with:

• DLG4^[10][11]
• NRG1,
• STAT5A,^[12][13] and
• YAP1.^[14]