Target name

Q15303: Receptor tyrosine-protein kinase erbB-4

  Protein 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.

  Database links

Uniprot primary ID Q15303
DrugBank ID DB08916
BioGrid ID 108378
PharmGKB ID PA27847
KEGG ID hsa:2066
Entrez Gene (Gene ID) 2066
DIP DIP-29650N
STRING 9606ENSP00000342235
MINT MINT-125091
IntAct Q15303
DMDM 3913590
BREDNA 27101
Rectome R-HSA-1250342 R-HSA-1257604 R-HSA-1250347 R-HSA-1963640 R-HSA-2219530 R-HSA-1963642 R-HSA-1250196 R-HSA-1227986 R-HSA-1236394 R-HSA-1253288 R-HSA-1251985 R-HSA-5673001
SignaLink Q15303
BindingDB Q15303

  Model Performance Metrics

Fingerprint type F1_CV AUC_CV Accuracy_CV Sensitivity_CV Specificity_CV F1_test AUC_test Accuracy_test Sensitivity_test Specificity_test Download model
FP2 fingerprints 0.842 0.889 0.852 0.780 0.925 0.914 0.947 0.927 0.941 0.917 Download
MACCS fingerprints 0.838 0.911 0.840 0.817 0.863 0.842 0.947 0.854 0.941 0.792 Download
Daylight fingerprints 0.859 0.877 0.870 0.780 0.963 0.941 0.950 0.951 0.941 0.958 Download
ECFP2 fingerprints 0.844 0.888 0.852 0.793 0.913 0.914 0.946 0.927 0.941 0.917 Download
ECFP4 fingerprints 0.870 0.919 0.877 0.817 0.938 0.909 0.968 0.927 0.882 0.958 Download
ECFP6 fingerprints 0.819 0.898 0.840 0.720 0.963 0.875 0.945 0.902 0.824 0.958 Download

  Download datasets

Positive dataset Negative dataset

Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

The recommended browsers: Safari, Firefox, Chrome,IE(Ver.>8).