| URN | urn:agi-llid:2066 |
|---|---|
| Total Entities | 0 |
| Connectivity | 766 |
| Name | ERBB4 |
| Description | v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) |
| Notes | A constitutively active ErbB4 mutant inhibits the formation of drug-resistant colonies by the DU-145 and PC-3 human prostate tumor cell lines A constitutively active ErbB4 mutant inhibits the formation of drug-resistant colonies by the DU-145 and PC-3 human prostate tumor cell lines. Absence of HER4 expression is associated with recurrence of ductal carcinoma in situ of the breast. Association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription. Data show that expression of the ErbB-4 ICD fragment leads to its constitutive association with and tyrosine phosphorylation of Mdm2. ErbB-4 characterization of the cleavage site and m80 fragment. ErbB4 expression was observed through all stages of chondrocytic differentiation in vitro. ErbB4 is increased by cAMP, a potent inducer of decidualization of the endometrial stroma. ErbB4 is specifically associated with neuritic plaques in the hippocampus of Alzheimer disease patients. Expression of HER4 protein correlates with favourable tumor stage in pancreatic cancer patients. HB-EGF may play a vital role in regulating luteal growth in a juxtacrine manner and through activating HER4 signalling. HER4 is involved in a non-proliferative or even protective role in breast cancer. Nuclear localization of the activated p80 fragment of Her-4 is associated with osteosarcoma pathogenesis. REsults report the 2.4 A crystal structure of the extracellular region of human ErbB4 in the absence of ligand and show that it adopts a tethered conformation similar to inactive forms of ErbB1 and ErbB3. The HER4/ERBB4 gene is a member of the type I receptor tyrosine kinase subfamily that includes EGFR (MIM 131550), ERBB2 (MIM 164870), and ERBB3 (MIM 190151). It encodes a receptor for NDF/heregulin (NRG1; MIM 142445).[supplied by OMIM]. WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity. YAP is a potential signaling partner of the full-length ErbB4 receptor at the membrane and of the COOH-terminal fragment of ErbB-4 that translocates to the nucleus to regulate transcription. Betacellulin may play a role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through EVT cell function via ErbB-4 in term placentas. Cleavage by gamma-secretase releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. Deletion of the PDZ domain recognition motif does abrogate the gamma-secretase cleavage of ErbB-4. ErbB receptor inactivation by unknown mechanisms results in altered splicing of bcl-x towards enhanced formation of proapoptotic Bcl-xS, thereby contributing to enhanced apoptotic susceptibility of failing human myocardium. Nuclear localization of STAT5A and stimulation of the beta-casein promoter requires nuclear translocation of the ERBB4 intracellular domain 4ICD; binding of the two proteins at transcription factor target promoters results in activation of gene expression. Proteolytic processing of ERBB4 is a critical event regulating multiple receptor signaling activities. |
| GO Molecular Function | receptor signaling protein tyrosine kinase activity |
|---|---|
| transmembrane receptor protein tyrosine kinase activity | |
| transferase activity | |
| transferase activity, transferring phosphorus-containing groups | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| epidermal growth factor receptor binding | |
| protein homodimerization activity | |
| nucleotide binding | |
| ATP binding | |
| transcription regulatory region DNA binding |
| GO Cellular Component | membrane |
|---|---|
| extracellular region | |
| membrane raft | |
| integral component of membrane | |
| caveola | |
| basolateral plasma membrane | |
| nucleoplasm | |
| nucleolus | |
| mitochondrial matrix | |
| postsynaptic density | |
| receptor complex | |
| plasma membrane | |
| cytoplasm | |
| cytosol | |
| mitochondrion | |
| nucleus |
| GO Biological Process | lactation |
|---|---|
| innate immune response | |
| Fc-epsilon receptor signaling pathway | |
| cell proliferation | |
| positive regulation of ERK1 and ERK2 cascade | |
| positive regulation of phosphatidylinositol 3-kinase activity | |
| multicellular organismal development | |
| embryonic pattern specification | |
| surfactant homeostasis | |
| positive regulation of cardiac muscle cell proliferation | |
| nervous system development | |
| heart development | |
| odontogenesis | |
| neural crest cell migration | |
| telencephalon development | |
| olfactory bulb interneuron differentiation | |
| mammary gland development | |
| mammary gland epithelial cell differentiation | |
| mammary gland alveolus development | |
| synapse maturation | |
| central nervous system morphogenesis | |
| cardiac muscle tissue regeneration | |
| cell fate commitment | |
| signal transduction | |
| positive regulation of tyrosine phosphorylation of Stat5 protein | |
| positive regulation of STAT protein import into nucleus | |
| phosphatidylinositol-mediated signaling | |
| neurotrophin TRK receptor signaling pathway | |
| transmembrane receptor protein tyrosine kinase signaling pathway | |
| fibroblast growth factor receptor signaling pathway | |
| epidermal growth factor receptor signaling pathway | |
| positive regulation of synaptic transmission, GABAergic | |
| cell migration | |
| positive regulation of cell migration | |
| regulation of cell migration | |
| apoptotic process | |
| negative regulation of apoptotic process | |
| mitochondrial fragmentation involved in apoptotic process | |
| negative regulation of muscle cell apoptotic process | |
| positive regulation of cell proliferation | |
| negative regulation of cell proliferation | |
| positive regulation of epithelial cell proliferation | |
| positive regulation of glucose import | |
| response to drug | |
| response to hydrogen peroxide | |
| response to progesterone | |
| positive regulation of transcription, DNA-templated | |
| positive regulation of protein phosphorylation | |
| regulation of transcription, DNA-templated | |
| transcription, DNA-templated | |
| protein phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| protein autophosphorylation | |
| phosphorylation |
| Pathway | Mechanism of Cetuximab Resistance in Colorectal Cancer |
|---|---|
| Multiple Myeloma Overview | |
| Proteins Involved in Pathogenesis of Breast Cancer Related to ERBB2/VEGFR/Akt Signaling Pathway | |
| Breast Cancer Related to ERBB/VEGFR/Akt Signaling Pathway | |
| ESR1/ERBB-positive Luminal Breast Cancer | |
| Mucinous Ovarian Carcinoma | |
| High-grade Serous Ovarian Carcinoma | |
| Endometrioid Ovarian Carcinoma | |
| Ovarian Cancer Overview | |
| Low-grade Serous Ovarian Carcinoma | |
| Type I Endometrial Cancer (Endometrioid Endometrial Cancer) | |
| Type II Endometrial Cancer (Clear-cell Endometrial Cancer and Papillary Serous Endometrial Cancer) | |
| Endometrial Cancer Overview | |
| Melanoma Overview | |
| Ependymoma | |
| Medulloblastoma Overview | |
| Proteins Involved in Pathogenesis of Medulloblastoma | |
| Impairment of EDN, NRG, NRTN, and GDNF/RET Signaling in Hirschsprung Disease | |
| Growth Factor Signaling in Pancreatic Cancer | |
| Pancreatic Ductal Carcinoma | |
| Pancreatic Neuroendocrine Tumors | |
| Growth Factor Signaling in Hepatocellular Carcinoma | |
| Hepatocellular Carcinoma Overview | |
| EGFR/ERBB -> STAT signaling | |
| DLL1 Expression Targets | |
| DLL4 Expression Targets | |
| AREG/STAT Expression Targets | |
| BTC/STAT Expression Targets | |
| EREG/STAT Expression Targets | |
| HBEGF/STAT Expression Targets | |
| NRG1/STAT Expression Targets | |
| TGFA/STAT Expression Targets | |
| NOTCH Expression Targets | |
| EGF/STAT Expression Targets | |
| epidermal growth factor/neuregulin signaling pathway |
| Group | GFR |
|---|---|
| Oncogenes | |
| lactation | |
| innate immune response | |
| Fc-epsilon receptor signaling pathway | |
| cell proliferation | |
| receptor signaling protein tyrosine kinase activity | |
| positive regulation of ERK1 and ERK2 cascade | |
| positive regulation of phosphatidylinositol 3-kinase activity | |
| multicellular organismal development | |
| embryonic pattern specification | |
| surfactant homeostasis | |
| positive regulation of cardiac muscle cell proliferation | |
| nervous system development | |
| heart development | |
| odontogenesis | |
| neural crest cell migration | |
| telencephalon development | |
| olfactory bulb interneuron differentiation | |
| mammary gland development | |
| mammary gland epithelial cell differentiation | |
| mammary gland alveolus development | |
| synapse maturation | |
| central nervous system morphogenesis | |
| cardiac muscle tissue regeneration | |
| cell fate commitment | |
| signal transduction | |
| positive regulation of tyrosine phosphorylation of Stat5 protein | |
| positive regulation of STAT protein import into nucleus | |
| phosphatidylinositol-mediated signaling | |
| transmembrane receptor protein tyrosine kinase activity | |
| neurotrophin TRK receptor signaling pathway | |
| transmembrane receptor protein tyrosine kinase signaling pathway | |
| fibroblast growth factor receptor signaling pathway | |
| epidermal growth factor receptor signaling pathway | |
| positive regulation of synaptic transmission, GABAergic | |
| cell migration | |
| positive regulation of cell migration | |
| regulation of cell migration | |
| apoptotic process | |
| negative regulation of apoptotic process | |
| mitochondrial fragmentation involved in apoptotic process | |
| negative regulation of muscle cell apoptotic process | |
| positive regulation of cell proliferation | |
| negative regulation of cell proliferation | |
| positive regulation of epithelial cell proliferation | |
| positive regulation of glucose import | |
| response to drug | |
| response to hydrogen peroxide | |
| response to progesterone | |
| positive regulation of transcription, DNA-templated | |
| positive regulation of protein phosphorylation | |
| regulation of transcription, DNA-templated | |
| transferase activity | |
| transferase activity, transferring phosphorus-containing groups | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| transcription, DNA-templated | |
| protein phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| protein autophosphorylation | |
| phosphorylation | |
| epidermal growth factor receptor binding | |
| protein homodimerization activity | |
| nucleotide binding | |
| ATP binding | |
| transcription regulatory region DNA binding | |
| membrane | |
| extracellular region | |
| membrane raft | |
| integral component of membrane | |
| caveola | |
| basolateral plasma membrane | |
| nucleoplasm | |
| nucleolus | |
| mitochondrial matrix | |
| postsynaptic density | |
| receptor complex | |
| plasma membrane | |
| cytoplasm | |
| cytosol | |
| mitochondrion | |
| nucleus | |
| Genes with Mutations, Deletions, and Amplifications Associated with Medulloblastoma | |
| Secreted proteins | |
| Biofluids assayable substances |
| LocusLink ID | 2066 |
|---|---|
| 13869 | |
| 59323 |
| Cell Localization | Plasma membrane |
|---|---|
| Cell membrane | |
| Nucleus | |
| Mitochondrion |
| GO ID | 0005524 |
|---|---|
| 0005154 | |
| 0042803 | |
| 0004713 | |
| 0004716 | |
| 0044212 | |
| 0004714 | |
| 0038095 | |
| 0061026 | |
| 0045165 | |
| 0016477 | |
| 0008283 | |
| 0021551 | |
| 0009880 | |
| 0007173 | |
| 0008543 | |
| 0007507 | |
| 0045087 | |
| 0007595 | |
| 0060749 | |
| 0060644 | |
| 0043653 | |
| 0043066 | |
| 0008285 | |
| 0007399 | |
| 0001755 | |
| 0048011 | |
| 0021889 | |
| 0018108 | |
| 0048015 | |
| 0070374 | |
| 2000366 | |
| 0060045 | |
| 0008284 | |
| 0043552 | |
| 0001934 | |
| 0045893 | |
| 0042523 | |
| 0046777 | |
| 0030334 | |
| 0007165 | |
| 0006351 | |
| 0007169 | |
| 0016323 | |
| 0005737 | |
| 0005829 | |
| 0005576 | |
| 0016021 | |
| 0005759 | |
| 0005739 | |
| 0005730 | |
| 0005654 | |
| 0005634 | |
| 0005886 | |
| 0016301 | |
| 0000166 | |
| 0004672 | |
| 0016740 | |
| 0016772 | |
| 0006915 | |
| 0007275 | |
| 0010656 | |
| 0016310 | |
| 0030335 | |
| 0050679 | |
| 0046326 | |
| 0032230 | |
| 0006468 | |
| 0006355 | |
| 0043129 | |
| 0060074 | |
| 0005901 | |
| 0016020 | |
| 0045121 | |
| 0014069 | |
| 0043235 | |
| 0030879 | |
| 0042476 | |
| 0042493 | |
| 0042542 | |
| 0032570 | |
| 0021537 | |
| 0005515 | |
| 0046982 | |
| 0004872 | |
| 0005887 | |
| 0009987 | |
| 0051726 | |
| 0005622 | |
| 0045768 | |
| 0005006 | |
| 0000074 | |
| 0050875 |
| Alias | HER4 |
|---|---|
| ALS19 | |
| p180erbB4 | |
| receptor tyrosine-protein kinase erbB-4 | |
| proto-oncogene-like protein c-ErbB-4 | |
| tyrosine kinase-type cell surface receptor HER4 | |
| v-erb-a erythroblastic leukemia viral oncogene homolog 4 | |
| avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4 | |
| c-erbB-4 | |
| AC167658.1 | |
| avian erythroblastosis oncogene B 4 | |
| receptor tyrosine kinase | |
| Tyro-2 | |
| Mer4 | |
| receptor tyrosine kinase ERB4 | |
| v-erb-a erythroblastic leukemia viral oncogene homolog IV | |
| v-erb-a avian erythroblastic leukemia viral oncogene homolog-like IV | |
| v-erb-a avian erythroblastic leukaemia viral oncogene homolog-like 4 | |
| v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 | |
| v-erb-a avian erythroblastic leukaemia viral oncogene homolog-like IV | |
| v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4 | |
| v-erb-a erythroblastic leukaemia viral oncogene homolog 4 | |
| v-erb-a erythroblastic leukaemia viral oncogene homolog 4 (avian) | |
| v-erb-a erythroblastic leukaemia viral oncogene homolog IV | |
| v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) | |
| epidermal growth factor receptor 4 | |
| ErbB4 receptor | |
| v-erb-b2 avian erythroblastic leukemia viral oncogene 4 | |
| OTTMUSP00000030427 | |
| avian erythroblastic leukaemia viral (v-erb-b2) oncogene homolog 4 | |
| avian erythroblastic leukaemia viral (v-erb-b2) oncogene homolog IV | |
| avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog IV | |
| avian erythroblastosis oncogene B IV | |
| epidermal growth factor receptor, HER | |
| OTTHUMP00000209432 | |
| OTTMUSP00000030425 | |
| ERB4 | |
| MGC138404 | |
| ERBB-4 receptor protein-tyrosine kinase | |
| Erbb4 | |
| ERB4_HUMAN | |
| OTTMUSP00000030426 | |
| ERBB-4 receptor protein-tyrosine kinase precursor |
| Mouse chromosome position | 1 33.8 cM |
|---|---|
| 1 35.1 cM |
| OMIM ID | 600543 |
|---|---|
| 615515 |
| Rat chromosome position | 9q32 |
|---|
| Hugo ID | 3432 |
|---|
| Human chromosome position | 2q33.3-q34 |
|---|
| Swiss-Prot Accession | Q15303 |
|---|---|
| Q61527 | |
| Q62956 | |
| Q6UA28 | |
| Q6UA29 | |
| Q9Z2N7 | |
| B2KGF5 | |
| B2KGF6 | |
| O88460 | |
| Q3UNS6 | |
| B7ZLD7 | |
| B7ZLE2 | |
| B7ZLE3 | |
| Q2M1W1 | |
| Q59EW4 | |
| O88459 | |
| Q53T57 | |
| Q580Q7 | |
| Q53R25 | |
| Q4ZG14 | |
| Q53QS8 | |
| Q53R48 |
| PIR ID | PT0184 |
|---|---|
| A47253 |
| Unigene ID | Hs.390729 |
|---|---|
| Mm.442420 | |
| Rn.163078 | |
| Mm.336982 | |
| Mm.387289 | |
| Hs.587035 | |
| Rn.42894 |
| KEGG ID | hsa:2066 |
|---|---|
| mmu:13869 | |
| rno:59323 |
| Swiss-Prot ID | ERBB4_RAT |
|---|---|
| ERBB4_MOUSE | |
| ERBB4_HUMAN |
| EC Number | 2.7.10.1 |
|---|
| Ensembl ID | ENSG00000178568 |
|---|---|
| ENSP00000403204 | |
| ENST00000436443 | |
| ENSP00000342235 | |
| ENST00000342788 | |
| ENSMUSG00000062209 | |
| ENSMUSP00000112713 | |
| ENSMUST00000119142 | |
| ENSRNOG00000014248 | |
| ENSRNOP00000019283 | |
| ENSRNOT00000019283 |
| Homologene ID | 21084 |
|---|
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| MGI ID | 104771 |
|---|
| RGD ID | 620486 |
|---|
| MedScan ID | 2066 |
|---|
| KEGG pathway | Calcium signaling pathway |
|---|---|
| Dorso-ventral axis formation |