| 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
| Disease | Target Count | P-value |
|---|---|---|
| Breast cancer | 3578 | 4.4e-57 |
| lung adenocarcinoma | 2716 | 4.4e-12 |
| Astrocytoma, Pilocytic | 3081 | 2.7e-08 |
| malignant mesothelioma | 3232 | 2.3e-07 |
| glioblastoma | 5792 | 1.6e-06 |
| osteosarcoma | 7950 | 3.8e-06 |
| tuberculosis | 2010 | 6.4e-05 |
| pituitary cancer | 1972 | 9.2e-05 |
| group 4 medulloblastoma | 1855 | 1.6e-04 |
| adult high grade glioma | 3801 | 1.9e-04 |
| astrocytic glioma | 2597 | 2.7e-03 |
| ependymoma | 4679 | 6.0e-03 |
| interstitial cystitis | 2312 | 7.9e-03 |
| oligodendroglioma | 2850 | 9.1e-03 |
| medulloblastoma, large-cell | 6241 | 2.0e-02 |
| pancreatic cancer | 2398 | 2.3e-02 |
| pancreatic carcinoma | 562 | 2.3e-02 |
| atypical teratoid / rhabdoid tumor | 5112 | 2.6e-02 |
| colon cancer | 1478 | 2.7e-02 |
| type II diabetes mellitus and post-ischemic heart failure | 88 | 2.8e-02 |
| nephrosclerosis | 333 | 3.9e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Asthma | 385 | 0.0 | 3.0 |
| Intestinal disease | 14 | 0.0 | 3.0 |
| Kidney disease | 430 | 0.0 | 0.9 |
| Osteoporosis | 363 | 0.0 | 2.4 |
| Thyroid cancer | 36 | 0.0 | 3.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| lung cancer | 4740 | 0.0 | 5.93517935373231E-5 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Cancer | 2499 | 3.837 | 1.9 |
| Hereditary spastic paraplegia 37 | 1 | 3.692 | 1.8 |
| Alzheimer's disease | 658 | 3.117 | 1.6 |
| Neuropathy | 261 | 3.107 | 1.6 |
| Heart disease | 306 | 3.032 | 1.5 |
| Disease | Target Count |
|---|---|
| Hirschsprung's disease | 46 |
| Disease | log2 FC | p |
|---|---|---|
| lung cancer | -2.400 | 5.9e-05 |
| adult high grade glioma | -2.100 | 1.9e-04 |
| astrocytic glioma | -2.000 | 2.7e-03 |
| Astrocytoma, Pilocytic | -2.900 | 2.7e-08 |
| atypical teratoid / rhabdoid tumor | 1.100 | 2.6e-02 |
| Breast cancer | -2.800 | 4.4e-57 |
| colon cancer | -1.200 | 2.7e-02 |
| ependymoma | -2.000 | 6.0e-03 |
| glioblastoma | -2.400 | 1.6e-06 |
| group 4 medulloblastoma | -2.200 | 1.6e-04 |
| interstitial cystitis | 1.800 | 7.9e-03 |
| lung adenocarcinoma | -1.400 | 4.4e-12 |
| malignant mesothelioma | 2.000 | 2.3e-07 |
| medulloblastoma, large-cell | -2.000 | 2.0e-02 |
| nephrosclerosis | -1.036 | 3.9e-02 |
| oligodendroglioma | -1.500 | 9.1e-03 |
| osteosarcoma | -1.817 | 3.8e-06 |
| pancreatic cancer | 1.100 | 2.3e-02 |
| pancreatic carcinoma | 1.100 | 2.3e-02 |
| pituitary cancer | 1.100 | 9.2e-05 |
| tuberculosis | 1.800 | 6.4e-05 |
| type II diabetes mellitus and post-ische... | 1.200 | 2.8e-02 |
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 //
