| URN | urn:agi-llid:2066 |
|---|---|
| Connectivity | 231 |
| 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. |
| Pathway | EGFR/ERBB -> STAT signaling |
|---|---|
| epidermal growth factor/neuregulin signaling pathway | |
| epidermal growth factor-neuregulin signaling pathway |
| GO Molecular Function | nucleotide binding |
|---|---|
| transferase activity | |
| ATP binding | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| receptor signaling protein tyrosine kinase activity | |
| transmembrane receptor protein tyrosine kinase activity | |
| receptor activity |
| GO Cellular Component | postsynaptic density |
|---|---|
| membrane | |
| plasma membrane | |
| cytoplasm | |
| membrane raft | |
| nucleus | |
| basolateral plasma membrane | |
| caveola | |
| integral to membrane |
| GO Biological Process | cell proliferation |
|---|---|
| positive regulation of anti-apoptosis | |
| synapse maturation | |
| telencephalon development | |
| cell fate commitment | |
| nervous system development | |
| heart development | |
| mammary gland development | |
| odontogenesis | |
| positive regulation of synaptic transmission, GABAergic | |
| signal transduction | |
| regulation of transcription | |
| positive regulation of epithelial cell proliferation | |
| positive regulation of cell migration | |
| transcription | |
| protein amino acid phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| response to drug | |
| response to hydrogen peroxide | |
| response to progesterone stimulus | |
| positive regulation of glucose import | |
| transmembrane receptor protein tyrosine kinase signaling pathway | |
| surfactant homeostasis |
| Ariadne Ontology | GFR |
|---|---|
| Oncogenes |
| Group | GFR |
|---|---|
| Oncogenes | |
| cell proliferation | |
| positive regulation of anti-apoptosis | |
| synapse maturation | |
| telencephalon development | |
| cell fate commitment | |
| nervous system development | |
| heart development | |
| mammary gland development | |
| odontogenesis | |
| positive regulation of synaptic transmission, GABAergic | |
| signal transduction | |
| regulation of transcription | |
| positive regulation of epithelial cell proliferation | |
| positive regulation of cell migration | |
| transcription | |
| protein amino acid phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| response to drug | |
| response to hydrogen peroxide | |
| response to progesterone stimulus | |
| positive regulation of glucose import | |
| transmembrane receptor protein tyrosine kinase signaling pathway | |
| surfactant homeostasis | |
| nucleotide binding | |
| transferase activity | |
| ATP binding | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| receptor signaling protein tyrosine kinase activity | |
| transmembrane receptor protein tyrosine kinase activity | |
| receptor activity | |
| postsynaptic density | |
| membrane | |
| plasma membrane | |
| cytoplasm | |
| membrane raft | |
| nucleus | |
| basolateral plasma membrane | |
| caveola | |
| integral to membrane |
| MedScan ID | 2066 |
|---|
| Hugo ID | 3432 |
|---|
| Human chromosome position | 2q33.3-q34 |
|---|
| LocusLink ID | 2066 |
|---|---|
| 13869 | |
| 59323 |
| Alias | HER4 |
|---|---|
| MGC138404 | |
| p180erbB4 | |
| receptor tyrosine-protein kinase erbB-4 | |
| OTTHUMP00000209432 | |
| proto-oncogene-like protein c-ErbB-4 | |
| tyrosine kinase-type cell surface receptor HER4 | |
| avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4 | |
| AC167658.1 | |
| c-erbB-4 | |
| OTTMUSP00000030425 | |
| OTTMUSP00000030426 | |
| OTTMUSP00000030427 | |
| avian erythroblastosis oncogene B 4 | |
| receptor tyrosine kinase | |
| Tyro-2 | |
| Mer4 | |
| 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 | |
| ERB4 | |
| ERB4_HUMAN | |
| Erbb4 | |
| ERBB-4 receptor protein-tyrosine kinase | |
| receptor tyrosine kinase ERB4 | |
| v-erb-a avian erythroblastic leukaemia viral oncogene homolog-like 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 avian erythroblastic leukemia viral oncogene homolog-like IV | |
| 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 | |
| v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) | |
| v-erb-a erythroblastic leukemia viral oncogene homolog IV | |
| ERBB-4 receptor protein-tyrosine kinase precursor |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| OMIM ID | 600543 |
|---|
| Mouse chromosome position | 1 35.1 cM |
|---|
| GO ID | 0005524 |
|---|---|
| 0000166 | |
| 0004872 | |
| 0004716 | |
| 0016740 | |
| 0004714 | |
| 0008283 | |
| 0030879 | |
| 0042476 | |
| 0018108 | |
| 0045768 | |
| 0030335 | |
| 0050679 | |
| 0046326 | |
| 0032230 | |
| 0045449 | |
| 0042493 | |
| 0042542 | |
| 0032570 | |
| 0007165 | |
| 0043129 | |
| 0060074 | |
| 0021537 | |
| 0007169 | |
| 0016323 | |
| 0005901 | |
| 0005737 | |
| 0016021 | |
| 0005634 | |
| 0005886 | |
| 0014069 | |
| 0016301 | |
| 0004672 | |
| 0004713 | |
| 0045165 | |
| 0007507 | |
| 0007399 | |
| 0006468 | |
| 0006350 | |
| 0016020 | |
| 0045121 | |
| 0005515 | |
| 0046982 | |
| 0007275 | |
| 0005887 | |
| 0009987 | |
| 0051726 | |
| 0005622 | |
| 0005006 | |
| 0000074 | |
| 0050875 |
| Rat chromosome position | 9q32 |
|---|
| Swiss-Prot Accession | Q15303 |
|---|---|
| Q4ZG14 | |
| Q53QS8 | |
| Q53R25 | |
| Q53R48 | |
| Q53T57 | |
| Q580Q7 | |
| B2KGF5 | |
| Q61527 | |
| O88459 | |
| Q62956 | |
| Q6UA27 | |
| Q6UA28 | |
| Q6UA29 | |
| Q9Z2N7 | |
| O88460 | |
| Q3UNS6 | |
| B7ZLD7 | |
| B7ZLE2 | |
| Q2M1W1 | |
| Q59EW4 |
| 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 |
| EC Number | 2.7.10.1 |
|---|
| Swiss-Prot ID | ERBB4_RAT |
|---|---|
| ERBB4_MOUSE | |
| ERBB4_HUMAN | |
| B2KGF5_MOUSE | |
| B7ZLD7_HUMAN |
| Cell Localization | Membrane |
|---|---|
| Plasma membrane |
| IPI ID | IPI00210292 |
|---|---|
| IPI00778194 | |
| IPI00122341 | |
| IPI00357770 | |
| IPI00896073 | |
| IPI00016371 | |
| IPI00215722 | |
| IPI00816395 | |
| IPI00229006 | |
| IPI00557667 | |
| IPI00778853 |
| Homologene ID | 21084 |
|---|
| RGD ID | 620486 |
|---|
| MGI ID | 104771 |
|---|
| KEGG pathway | Calcium signaling pathway |
|---|---|
| Dorso-ventral axis formation |