ERBB4 [The Human Chemical-Genetic Interaction Map Project]

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======= ERBB4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ERBB4
  * **<color #00a2e8>Official Name</color>**: erb-b2 receptor tyrosine kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2066|2066]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q15303|Q15303]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ERBB4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ERBB4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600543|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, 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 and other factors and 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. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Recep L domain|
|Furin-like|
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|central nervous system morphogenesis|
|cardiac muscle tissue regeneration|
|mitochondrial fragmentation involved in apoptotic process|
|negative regulation of neuron migration|
|olfactory bulb interneuron differentiation|
|mammary gland epithelial cell differentiation|
|positive regulation of protein localization to cell surface|
|mammary gland lobule development|
|mammary gland alveolus development|
|positive regulation of cardiac muscle cell proliferation|
|ERBB2 signaling pathway|
|olfactory bulb development|
|epidermal growth factor receptor binding|
|olfactory lobe development|
|positive regulation of cardiac muscle tissue growth|
|basal plasma membrane|
|positive regulation of heart growth|
|regulation of protein localization to cell surface|
|regulation of cardiac muscle cell proliferation|
|regulation of neuron migration|
|cellular response to epidermal growth factor stimulus|
|positive regulation of cardiac muscle tissue development|
|lactation|
|response to epidermal growth factor|
|positive regulation of organ growth|
|integral component of postsynaptic density membrane|
|forebrain neuron differentiation|
|neural crest cell migration|
|transmembrane receptor protein tyrosine kinase activity|
|mammary gland epithelium development|
|integral component of presynaptic membrane|
|regulation of cardiac muscle tissue growth|
|apoptotic mitochondrial changes|
|embryonic pattern specification|
|tissue regeneration|
|regulation of heart growth|
|forebrain generation of neurons|
|GABA-ergic synapse|
|positive regulation of tyrosine phosphorylation of STAT protein|
|positive regulation of striated muscle tissue development|
|positive regulation of muscle organ development|
|ERBB signaling pathway|
|positive regulation of muscle tissue development|
|body fluid secretion|
|neural crest cell development|
|regulation of tyrosine phosphorylation of STAT protein|
|regulation of cardiac muscle tissue development|
|stem cell development|
|mesenchymal cell development|
|positive regulation of receptor signaling pathway via JAK-STAT|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|positive regulation of receptor signaling pathway via STAT|
|protein tyrosine kinase activity|
|neural crest cell differentiation|
|regulation of organ growth|
|synapse assembly|
|regulation of phosphatidylinositol 3-kinase signaling|
|mammary gland development|
|regulation of receptor signaling pathway via JAK-STAT|
|regulation of striated muscle tissue development|
|regulation of receptor signaling pathway via STAT|
|regulation of muscle tissue development|
|regulation of muscle organ development|
|peptidyl-tyrosine phosphorylation|
|peptidyl-tyrosine modification|
|regeneration|
|mesenchymal cell differentiation|
|stem cell differentiation|
|positive regulation of protein kinase B signaling|
|positive regulation of developmental growth|
|ameboidal-type cell migration|
|central nervous system neuron differentiation|
|positive regulation of peptidyl-tyrosine phosphorylation|
|protein autophosphorylation|
|basolateral plasma membrane|
|postsynaptic membrane|
|receptor complex|
|positive regulation of ERK1 and ERK2 cascade|
|transcription regulatory region DNA binding|
|regulation of protein kinase B signaling|
|mesenchyme development|
|cell fate commitment|
|regulation of peptidyl-tyrosine phosphorylation|
|telencephalon development|
|positive regulation of growth|
|negative regulation of cell migration|
|synapse organization|
|negative regulation of cell motility|
|negative regulation of neurogenesis|
|regulation of ERK1 and ERK2 cascade|
|negative regulation of cellular component movement|
|negative regulation of nervous system development|
|negative regulation of locomotion|
|positive regulation of cellular protein localization|
|regulation of developmental growth|
|negative regulation of cell development|
|glutamatergic synapse|
|mitochondrial matrix|
|MAPK cascade|
|forebrain development|
|developmental growth|
|growth|
|signal transduction by protein phosphorylation|
|gland development|
|pattern specification process|
|mitochondrion organization|
|wound healing|
|regulation of body fluid levels|
|cellular response to growth factor stimulus|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|heart development|
|response to growth factor|
|regulation of cellular protein localization|
|positive regulation of MAPK cascade|
|response to wounding|
|regulation of growth|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|brain development|
|regulation of MAPK cascade|
|head development|
|regulation of neurogenesis|
|regulation of cell migration|
|circulatory system development|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|cell migration|
|protein phosphorylation|
|embryo development|
|central nervous system development|
|regulation of locomotion|
|regulation of cellular component movement|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|programmed cell death|
|positive regulation of phosphorylation|
|localization of cell|
|cell motility|
|cell death|
|epithelium development|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of multicellular organismal process|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|mitochondrion|
|phosphorylation|
|locomotion|
|positive regulation of developmental process|
|integral component of plasma membrane|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|movement of cell or subcellular component|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|positive regulation of signal transduction|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 14102
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -1.17 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ERBB4 Expression in NALM6 Cells: -1.17'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>