| URN | urn:agi-llid:2065 |
|---|---|
| Connectivity | 221 |
| Name | Erbb3 |
| Description | v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) |
| Notes | AP-2gamma is important in the regulation of Erbb-3 expression in human mammary epithelial and lung fibroblast cells AP-2gamma is important in the regulation of Erbb-3 expression in human mammary epithelial and lung fibroblast cells. Activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas. Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed. ERBB2 and ERBB3 expression is inhibited by quercetin, resulting in decreased autophosphorylation and cell growth. Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers. ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation. ErbB3 is an obligate heterodimerization partner because of its inability to homodimerize. ErbB3 is involved in IFN-alpha-induced proliferation of myeloma cells. ErbB3 proteins are promising targets for therapy, and siRNAs may be useful for this purpose. Expression of epidermal growth factor receptor, erbB2, and erbB3, but not erbB4, was detected throughout the epidermis. Labeling for erbB2 and erbB3 accentuated in upper spinous layers. Inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of this epidermal growth factor receptor family member. Overexpression of ErbB3 is associated with transitional cell carcinoma of the bladder. Potential of anti-HER3 antibodies for the therapy of breast cancer and other malignancies characterized by overexpression of HER3. Role of the N-terminus of epidermal growth factor in binding studied by phage display. These results suggest that ErbB3 expression alone does not uniquely confer IFN-alpha growth responsiveness, but instead may amplify proliferation rates in MM cells that have acquired atypical expression of this receptor. This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. This review summarizes evidence of defective expression of erbB3 in the prefrontal cortex of schizophrenic patients, implicating erbB3 involvement in the pathogenesis of schizophrenia. Transcriptional activity of eztrogen receptor beta was altered in a manner similar to ERalpha by activation of ErbB2/ErbB3. Before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-beta is cleaved and binds to human epidermal growth factor receptor 3. Calculated binding free energies between the N-SH2 domain of PI-3 kinase and P-peptides generated by erbb3 showed excellent qualitative agreement with SPR data with a correlation coefficient of 0.91. Heterodimer formation with heregulin regulates erbB2 receptor. Most of the ErbB3-ECD on the cell surface is apparently kept in an open conformation through oligomerization. Role of overexpression in lung cancer development in conjunction with erb-B-2 overexpression. Structure reveals a contact between domains II and IV that constrains the relative orientations of ligand-binding domains. The ErbB-3 affinity of a ligand determines whether it can form only ErbB-2/ErbB-3 complexes or also ErbB-3 homodimers. |
| Pathway | ERBB2/3 -> EP300/ETS/ETV/SP1 signaling |
|---|---|
| EGFR/ERBB3 -> MEF/MYOD/NFATC/MYOG signaling | |
| epidermal growth factor/neuregulin signaling pathway | |
| epidermal growth factor-neuregulin signaling pathway |
| GO Molecular Function | nucleotide binding |
|---|---|
| transferase activity | |
| growth factor binding | |
| protein homodimerization activity | |
| protein heterodimerization activity | |
| ATP binding | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| receptor signaling protein tyrosine kinase activity | |
| transmembrane receptor protein tyrosine kinase activity | |
| protein tyrosine kinase activator activity | |
| receptor activity | |
| transmembrane receptor activity |
| GO Cellular Component | extracellular region |
|---|---|
| postsynaptic membrane | |
| membrane | |
| extracellular space | |
| plasma membrane | |
| nucleus | |
| basolateral plasma membrane | |
| apical plasma membrane | |
| lateral plasma membrane | |
| integral to membrane | |
| integral to plasma membrane | |
| receptor complex |
| GO Biological Process | regulation of cell proliferation |
|---|---|
| circadian rhythm | |
| peripheral nervous system development | |
| cranial nerve development | |
| heart development | |
| tongue development | |
| skeletal muscle tissue development | |
| axonogenesis | |
| Schwann cell differentiation | |
| odontogenesis | |
| mammary gland involution | |
| signal transduction | |
| negative regulation of cell adhesion | |
| negative regulation of signal transduction | |
| positive regulation of phosphoinositide 3-kinase cascade | |
| phosphoinositide 3-kinase cascade | |
| negative regulation of neuron apoptosis | |
| protein amino acid phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| cellular response to insulin stimulus | |
| neuron apoptosis | |
| response to drug | |
| response to wounding | |
| wound healing | |
| negative regulation of secretion | |
| positive regulation of glucose import | |
| transmembrane receptor protein tyrosine kinase signaling pathway |
| Ariadne Ontology | GFR |
|---|---|
| Oncogenes |
| Group | GFR |
|---|---|
| Oncogenes | |
| extracellular region | |
| regulation of cell proliferation | |
| circadian rhythm | |
| peripheral nervous system development | |
| cranial nerve development | |
| heart development | |
| tongue development | |
| skeletal muscle tissue development | |
| axonogenesis | |
| Schwann cell differentiation | |
| odontogenesis | |
| mammary gland involution | |
| signal transduction | |
| negative regulation of cell adhesion | |
| negative regulation of signal transduction | |
| positive regulation of phosphoinositide 3-kinase cascade | |
| phosphoinositide 3-kinase cascade | |
| negative regulation of neuron apoptosis | |
| protein amino acid phosphorylation | |
| peptidyl-tyrosine phosphorylation | |
| cellular response to insulin stimulus | |
| neuron apoptosis | |
| response to drug | |
| response to wounding | |
| wound healing | |
| negative regulation of secretion | |
| positive regulation of glucose import | |
| transmembrane receptor protein tyrosine kinase signaling pathway | |
| nucleotide binding | |
| transferase activity | |
| growth factor binding | |
| protein homodimerization activity | |
| protein heterodimerization activity | |
| ATP binding | |
| kinase activity | |
| protein kinase activity | |
| protein tyrosine kinase activity | |
| receptor signaling protein tyrosine kinase activity | |
| transmembrane receptor protein tyrosine kinase activity | |
| protein tyrosine kinase activator activity | |
| receptor activity | |
| transmembrane receptor activity | |
| postsynaptic membrane | |
| membrane | |
| extracellular space | |
| plasma membrane | |
| nucleus | |
| basolateral plasma membrane | |
| apical plasma membrane | |
| lateral plasma membrane | |
| integral to membrane | |
| integral to plasma membrane | |
| receptor complex |
| MedScan ID | 2065 |
|---|
| Hugo ID | 3431 |
|---|
| Human chromosome position | 12q13 |
|---|
| LocusLink ID | 2065 |
|---|---|
| 13867 | |
| 29496 | |
| 13868 | |
| 97627 |
| Alias | HER3 |
|---|---|
| LCCS2 | |
| ErbB-3 | |
| c-erbB3 | |
| erbB3-S | |
| MDA-BF-1 | |
| MGC88033 | |
| c-erbB-3 | |
| p180-ErbB3 | |
| p45-sErbB3 | |
| p85-sErbB3 | |
| receptor tyrosine-protein kinase erbB-3 | |
| proto-oncogene-like protein c-ErbB-3 | |
| tyrosine kinase-type cell surface receptor HER3 | |
| v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 | |
| C76256 | |
| Erbb3r | |
| MGC117742 | |
| receptor tyrosine kinase | |
| glial growth factor receptor | |
| avian erythroblastosis oncogene B 3 receptor | |
| avian erythroblastosis oncogene B 3 | |
| avian erythroblastosis oncogene B 3 receptors | |
| avian erythroblastosis oncogene B III | |
| ERB3 | |
| ERB3_HUMAN | |
| Erbb3 | |
| ERBB-3 receptor protein-tyrosine kinase | |
| ErbB3/Her3 | |
| HER3 kinase | |
| lethal congenital contracture syndrome 2 | |
| Transformation gene ERBB III | |
| Transformation gene ERBB-3 | |
| v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog 3 | |
| v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog III | |
| v-erb-b2 avian erythroblastic leukemia viral oncogene homolog III | |
| v-erb-b2 erythroblastic leukaemia viral oncogene homolog 3 | |
| v-erb-b2 erythroblastic leukaemia viral oncogene homolog 3 (avian) | |
| v-erb-b2 erythroblastic leukaemia viral oncogene homolog III | |
| v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 | |
| v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) | |
| v-erb-b2 erythroblastic leukemia viral oncogene homolog III | |
| ERBB-3 receptor protein-tyrosine kinase precursor | |
| ErbB3/Her3 precursor | |
| lethal congenital contracture syndrome type 2 | |
| C76256s | |
| expressed sequence C76256 |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| OMIM ID | 190151 |
|---|---|
| 607598 |
| Mouse chromosome position | 10 70.0 cM |
|---|
| GO ID | 0005524 |
|---|---|
| 0019838 | |
| 0000166 | |
| 0046982 | |
| 0042803 | |
| 0030296 | |
| 0004713 | |
| 0004716 | |
| 0016740 | |
| 0004888 | |
| 0004714 | |
| 0014037 | |
| 0007409 | |
| 0032869 | |
| 0007623 | |
| 0021545 | |
| 0007507 | |
| 0060056 | |
| 0007162 | |
| 0043524 | |
| 0051048 | |
| 0009968 | |
| 0051402 | |
| 0042476 | |
| 0007422 | |
| 0014065 | |
| 0046326 | |
| 0014068 | |
| 0006468 | |
| 0042127 | |
| 0042493 | |
| 0007165 | |
| 0007519 | |
| 0043586 | |
| 0007169 | |
| 0042060 | |
| 0016324 | |
| 0016323 | |
| 0005576 | |
| 0005615 | |
| 0005887 | |
| 0016328 | |
| 0005634 | |
| 0005886 | |
| 0045211 | |
| 0043235 | |
| 0016301 | |
| 0004672 | |
| 0004872 | |
| 0016021 | |
| 0016020 | |
| 0018108 | |
| 0009611 | |
| 0005515 | |
| 0051726 | |
| 0005622 | |
| 0005006 | |
| 0004674 | |
| 0000074 | |
| 0050875 |
| Rat chromosome position | 7q11 |
|---|
| Swiss-Prot Accession | P21860 |
|---|---|
| B3KWG5 | |
| O75810 | |
| O75811 | |
| O75812 | |
| O75813 | |
| Q9BUD7 | |
| Q9NNX2 | |
| Q61526 | |
| O88458 | |
| Q62799 | |
| Q62955 | |
| Q3KQR1 | |
| Q68J64 | |
| Q810U8 | |
| Q8K317 |
| PIR ID | JC4387 |
|---|---|
| A36223 | |
| JH0803 |
| Unigene ID | Hs.118681 |
|---|---|
| Mm.373043 | |
| Rn.10228 | |
| Hs.567263 | |
| Mm.29023 |
| KEGG ID | hsa:2065 |
|---|---|
| mmu:13867 | |
| rno:29496 |
| EC Number | 2.7.10.1 |
|---|---|
| 2.7.1.112 |
| Swiss-Prot ID | ERBB3_RAT |
|---|---|
| ERBB3_MOUSE | |
| ERBB3_HUMAN | |
| B3KWG5_HUMAN |
| Cell Localization | Membrane |
|---|---|
| Cell membrane | |
| Secreted | |
| Plasma membrane |
| IPI ID | IPI00208301 |
|---|---|
| IPI00468814 | |
| IPI00219206 | |
| IPI00298285 | |
| IPI00794366 | |
| IPI00815836 | |
| IPI00816069 | |
| IPI00815996 | |
| IPI00815859 | |
| IPI00871990 | |
| IPI00791489 | |
| IPI00792591 | |
| IPI00792105 | |
| IPI00793752 | |
| IPI00793243 |
| Homologene ID | 20457 |
|---|
| RGD ID | 69323 |
|---|
| MGI ID | 95411 |
|---|---|
| 2143908 |
| KEGG pathway | Calcium signaling pathway |
|---|