| Tbio | Pro-neuregulin-1, membrane-bound isoform |
Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity).
The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]
The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]
Comments
Property Summary
| NCBI Gene PubMed Count | 409 |
| Grant Count | 540 |
| R01 Count | 264 |
| Funding | $62,677,623.4 |
| PubMed Score | 843.84 |
| PubTator Score | 761.38 |
| Disease | log2 FC | p |
|---|---|---|
| nephrosclerosis | -1.036 | 0.039 |
| pancreatic cancer | 1.100 | 0.023 |
| malignant mesothelioma | 2.100 | 0.000 |
| astrocytic glioma | -2.000 | 0.003 |
| posterior fossa group A ependymoma | -2.200 | 0.000 |
| oligodendroglioma | -1.500 | 0.009 |
| osteosarcoma | -1.817 | 0.000 |
| glioblastoma | -2.600 | 0.001 |
| type II diabetes mellitus and post-ische... | 1.200 | 0.028 |
| atypical teratoid / rhabdoid tumor | 1.100 | 0.026 |
| group 4 medulloblastoma | -2.200 | 0.000 |
| medulloblastoma, large-cell | -2.000 | 0.020 |
| tuberculosis | 1.900 | 0.000 |
| colon cancer | -1.200 | 0.027 |
| lung cancer | -2.400 | 0.000 |
| interstitial cystitis | 1.800 | 0.008 |
| lung adenocarcinoma | -1.500 | 0.000 |
| pediatric high grade glioma | -2.100 | 0.001 |
| pilocytic astrocytoma | -3.000 | 0.000 |
| pancreatic carcinoma | 1.100 | 0.023 |
| Breast cancer | -2.800 | 0.000 |
| pituitary cancer | 2.000 | 0.000 |
| PMID | Text |
|---|---|
| 27110055 | Study shows that Neuregulin did not perform successfully as a biomarker for acute myocardial infarction or acute coronary syndrome in the emergency department. |
| 26891847 | This study demonstrate dysregulation of the NRG1-ErbB4/3 axis in both human and mouse ALS and to provide support for NRG1 supplementation as a possible therapeutic option for motor neuron disease |
| 26886748 | while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, hepatitis c virus induced a substantial reduction of ErbB3 and ErbB4 expression. |
| 26780728 | In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. |
| 26648299 | NRG1 promotes the proliferation and migration of coronary artery smooth muscle cells by enhancing the phosphorylation of ErbB2, ErbB3 and ErbB4. |
| 26588216 | Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype |
| 26535009 | Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. |
| 26534905 | Polymorphisms of dopamine pathway gene NRG1 is associated with cognitive performance in Bipolar disorder. |
| 26490994 | findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development. |
| 26327598 | Data indicate telomere-binding protein RAP1 as an interacting partner of isoform beta2 of the heregulin (HRGbeta2). |
| More... |
MSERKEGRGKGKGKKKERGSGKKPESAAGSQSPALPPRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKW 1 - 70 FKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDSASANITIVESNEIITGMP 71 - 140 ASTEGAYVSSESPIRISVSTEGANTSSSTSTSTTGTSHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLC 141 - 210 KCQPGFTGARCTENVPMKVQNQEKAEELYQKRVLTITGICIALLVVGIMCVVAYCKTKKQRKKLHDRLRQ 211 - 280 SLRSERNNMMNIANGPHHPNPPPENVQLVNQYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTTVTQT 281 - 350 PSHSWSNGHTESILSESHSVIVMSSVENSRHSSPTGGPRGRLNGTGGPRECNSFLRHARETPDSYRDSPH 351 - 420 SERYVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVSMPSMAVSPFMEEERPLLLVTPPRLREKK 421 - 490 FDHHPQQFSSFHHNPAHDSNSLPASPLRIVEDEEYETTQEYEPAQEPVKKLANSRRAKRTKPNGHIANRL 491 - 560 EVDSNTSSQSSNSESETEDERVGEDTPFLGIQNPLAASLEATPAFRLADSRTNPAGRFSTQEEIQARLSS 561 - 630 VIANQDPIAV 631 - 640 //
| PMID | Year | Title |
|---|---|---|
| 27110055 | 2016 | Diagnostic Utility of Neuregulin for Acute Coronary Syndrome. |
| 27027665 | 2016 | Gene aberrations for precision medicine against lung adenocarcinoma. |
| 26993800 | 2016 | Neuregulin-1 controls an endogenous repair mechanism after spinal cord injury. |
| 26960157 | 2016 | Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway. |
| 26909665 | 2016 | Effects of NRG1 genotypes on orbitofrontal sulcogyral patterns in Japanese patients diagnosed with schizophrenia. |
| 26891847 | 2016 | Neuregulin 1 confers neuroprotection in SOD1-linked amyotrophic lateral sclerosis mice via restoration of C-boutons of spinal motor neurons. |
| 26886748 | 2016 | Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family. |
| 26780728 | 2016 | Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells. |
| 26648299 | 2015 | [Neuregulin-1 promotes proliferation and migration of human coronary artery smooth muscle cells by enhancing its receptor phosphorylation]. |
| 26588216 | 2015 | Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation. |
| More... |
