Recombinant Human Pro-neuregulin-1, membrane-bound isoform(NRG1),partial(Active)

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Code CSB-AP002851HU
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Product Details

Purity >97% as determined by SDS-PAGE and HPLC.
Endotoxin Less than 1.0 EU/μg as determined by LAL method.
Activity Fully biologically active when compared to standard. The ED50 as determined by a cell proliferation assay using serum free human MCF-7 cells is less than 0.5 ng/ml, corresponding to a specific activity of >2.0x106 IU/mg.
Target Names NRG1
Uniprot No. Q02297
Research Area Neuroscience?
Alternative Names Acetylcholine receptor-inducing activity; Acetylcholine receptor-inducing activity, chick, homolog of; ARIA; Breast cancer cell differentiation factor p45; GGF; GGF2; glial growth factor 2; Glial growth factor; Heregulin; heregulin, alpha (45kD, ERBB2 p185-activator); heregulin, alpha; HGL; HRG; HRG1; HRGA; MST131; MSTP131; NDF; Neu differentiation factor; Neuregulin-1; nrg1; NRG1-IT2; NRG1_HUMAN; Pro-NRG1; Sensory and motor neuron-derived factor; SMDF
Species Homo sapiens (Human)
Source E.coli
Expression Region 122-186aa
Complete Sequence SHLVKCAEKE KTFCVNGGEC FMVKDLSNPS RYLCKCPNEF TGDRCQNYVM ASFYKHLGIE FMEAE
Mol. Weight 7.5 kDa
Protein Length Partial of Isoform 11
Tag Info Tag-Free
Form Lyophilized powder
Buffer Lyophilized from a 0.2 m filtered 1 × PBS, pH 7.4, with 5 % trehalose
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Basically, we can dispatch the products out in 5-10 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

Target Data

Function 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
Gene References into Functions
  1. Enhanced ERBB4 phosphorylation could mediate NRG1 effects on mitochondrial function through signalling pathways PMID: 28496106
  2. In Autism Spectrum Disorder patients, the NRG1 levels were found to be statistically significantly high compared to the healthy control group. PMID: 30150060
  3. COMT-GG and NRG1-AA genotypes aid the transcranial direct current stimulation-induced improvement in auditory verbal hallucinations in schizophrenia patients. PMID: 29559020
  4. The neuregulin1 was observed to be cleaved, adding to the 3 known NS3/4A cleavage targets. It showed that NS3/4A triggers an increase in neuregulin1 mRNA levels in HCV infected cells. PMID: 29438748
  5. These results support the association between genetic variation of RET and NRG1 and susceptibility to Hirschsprung disease in the Chinese population. PMID: 28256518
  6. Results found that NRG1, a potential prognostic marker is highly expressed in papillary thyroid cancer (PTC). Also, further data demonstrate that NRG1 activates the antioxidant pathway by upregulating the expression of antioxidant enzymes through NRF2, thus modulating redox homeostasis in PTC. PMID: 29901070
  7. Mesenchymal stem cell-drived paclitaxel resistance in ErbB2/ErbB3-coexpressing breast cancer cells could be attributed to upregulation of Survivin via paracrine effect of NRG-1/ErbB3/PI-3K/Akt signaling, as either specific knockdown expression of ErbB3, or blocking of downstream PI-3K/Akt signaling, or specific inhibition of Survivin can completely reverse this effect. PMID: 29715459
  8. The data suggest a role for transcriptional regulation of NRG1 in the predisposition to papillary thyroid carcinoma. PMID: 29121253
  9. NRG1rs3924999 and NRG1 rs6994992 are associated with change of temperament scores in a clinical sample of subjects with major depression (MDD), who received selective serotonin reuptake inhibitor treatment. PMID: 29310728
  10. NRG1 is a potential prognostic and therapeutic biomarker in gastric cancer patients PMID: 28573357
  11. Study found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex of patients with symptomatic epilepsy. Also, NRG1-ErbB4 signaling suppresses GluN2B phosphorylation by Src inhibition. GluN2B is closely related to synaptic activity and its regulation by the NRG1-ErbB4-Src signaling axis highlights the importance of NRG1-ErbB4 signaling in symptomatic epilepsy pathology. PMID: 28273943
  12. Levels of NRG1 type III expression in peripheral blood mononuclear cells were positively correlated with impairments in social interaction in children with autism spectrum disorder. PMID: 28089559
  13. NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-overexpressing breast cancer cells. HER3 monoclonal antibody combined with trastuzumab may serve as a treatment choice for patients with primary resistance to trastuzumab. PMID: 29048656
  14. Results represent the first comprehensive investigation of neuregulin-1 (NRG1) isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia. PMID: 29225331
  15. HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer PMID: 27941874
  16. Date indicate the subcellular localization and dynamics post-translational processing, (ectodomain shedding) of neuregulin1 (NRG1). PMID: 27364328
  17. NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls. PMID: 28430337
  18. The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. PMID: 28600476
  19. Using time-resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies is decreased. PMID: 28507002
  20. Data suggest that SLC3A2-NRG1 should be considered a therapeutic target for patients with invasive mucinous adenocarcinoma of the lung (IMA). PMID: 27626312
  21. we show that ErbB3 interacts with the ESCRT-0 subunit Hrs both in the presence and absence of heregulin. This indicates an ESCRT-mediated sorting of ErbB3 to late endosomes and lysosomes, and in line with this we show that impaired ESCRT function leads to an endosomal accumulation of ErbB3. PMID: 28867611
  22. NRG1 genotype is associated with substance use. PMID: 27353026
  23. Significant genetic risk for Hirschsprung disease (HSCR) was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3 in a Chinese population. No evidence was found of a genetic association between HSCR and either of the NRG1 SNPs rs7835688 and rs16879552, at either allele or genotype level. PMID: 27203398
  24. High HRG1 expression is associated with breast cancer. PMID: 26885614
  25. Results showed that heregulin-1ss mRNA was downregulated in 82 % of patients with hepatocellular carcinoma. PMID: 27514687
  26. NRG1/ErbB2/Src/PTK2 signaling pathway may be a novel regulator of keloid fibroblast migration. PMID: 27882385
  27. The plasma soluble NRG1 level was significantly higher in mild and moderate Alzheimer's disease patients compared to controls. PMID: 27133777
  28. Data indicate a role for AXL receptor tyrosine kinase (AXL) in regulating the nuclear translocation of epidermal growth factor receptor (EGFR) and suggest that AXL-mediated SRC family kinases (SFKs) and neuregulin-1 (NRG1) expression promote this process. PMID: 28049763
  29. NRG1FISH detection should be considered in patients with IMA pan-negative for known driver oncogenes. These results might suggest that NRG1 fusion is more frequent in IMA from Asian patient. PMID: 27770508
  30. Results suggest genetic variation at the 5' and 3' ends of NRG1 are associated with schizophrenia. [Meta-Analysis] PMID: 28094814
  31. Nrg1 acts as an axonal signal that drives virtually all stages of Schwann cell development and myelination.Nrg1 plays important role in the peripheral nerve injury and nerve repair.[review] PMID: 26970613
  32. We also demonstrate that the effects of RET and NRG1 are universal across European and Asian ancestries. In contrast, we detected a European-specific association of a low-frequency variant, rs80227144, in SEMA3. Conditional analyses on the lead SNPs revealed a secondary association signal, corresponding to an Asian-specific, low-frequency missense variant encoding RET p.Asp489Asn PMID: 27702942
  33. primary aromatase inhibitor treatment modulates expression of HER-family members as well as EGFR1 and NRG1 in HER-2/neu non-amplified breast cancers in vivo PMID: 27343990
  34. GGF2 may improve contractile performance in the failing rat heart and that infrequent exposure to GGF2 may improve LV function PMID: 27993643
  35. these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD. PMID: 27486021
  36. Orbitofrontal sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment. PMID: 26909665
  37. This study found a significant association between genetic variation at NRG1 and the modulation of small-worldness properties of the functional cortical network during the performance of an odd-ball task in healthy subjects. PMID: 26650688
  38. Neuregulin-1 has now been accepted to have therapeutic potential in cardiovascular disease. The preclinical and clinical researches of NRG1 have demonstrated its advantage effects in cardiac function with multi-target cardiovascular biology and pathophysiology, but its influence on cardiac electrophysiology is rarely involved, which is a very important aspect and should not be ignored. [review] PMID: 26902151
  39. Results suggest that silibinin is a potential anti-cancer drug to inhibit proliferative and invasive characteristics of the epithelial ovarian cancer (EOC) cells that exhibit an autocrine heregulin (HRG)/HER3 protein (HRG/HER3) pathway. PMID: 26482609
  40. This population-based case-control study was carried out to determine whether polymorphisms in DISC1 and NRG1 genes could be associated with schizophrenia in the Chinese population. PMID: 27236031
  41. SZuggest the use of polymeric PLGA and PEG-PLGA microparticles as delivery systems for NRG1 in the treatment of myocardial infarction. PMID: 26546270
  42. NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. PMID: 26888291
  43. overexpression of phospho-ALK and alternative receptor tyrosine kinases such as phospho-EGFR, phospho-HER3, and phospho-IGFR-1R was observed in both resistant cell lines. Additionally, NRG1, a ligand for HER3, is upregulated and responsible for resistance by activating the EGFR family pathways through the NRG1-HER3-EGFR axis. PMID: 26992917
  44. Study found significant association between NRG1 (rs35753505) gene polymorphism and the risk of temporal lobe epilepsy in a Chinese Han population PMID: 26071373
  45. Study shows that Neuregulin did not perform successfully as a biomarker for acute myocardial infarction or acute coronary syndrome in the emergency department. PMID: 27110055
  46. 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 PMID: 26891847
  47. Data show that isoform beta2 of the heregulin (HRGbeta2) localizes at telomeres with the telomere-associated proteins TRF2 and RAP1. PMID: 26318724
  48. Data indicate telomere-binding protein RAP1 as an interacting partner of isoform beta2 of the heregulin (HRGbeta2). PMID: 26327598
  49. findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development. PMID: 26490994
  50. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. PMID: 26535009
  51. 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. PMID: 26886748
  52. Polymorphisms of dopamine pathway gene NRG1 is associated with cognitive performance in Bipolar disorder. PMID: 26534905
  53. NRG1 promotes the proliferation and migration of coronary artery smooth muscle cells by enhancing the phosphorylation of ErbB2, ErbB3 and ErbB4. PMID: 26648299
  54. 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. PMID: 26780728
  55. Heregulin-ErbB3-Driven Tumor Growth Persists in PI3 Kinase Mutant Cancer Cells. PMID: 26116360
  56. both ErbB-2 and ErbB-3 receptors are expressed in colon cancer stem cells and NRG-1beta plays an important role in sustaining proliferation of both wild-type and BRAF-V600E mutated cells PMID: 26160848
  57. findings suggest that inflammasome-induced alveolar cell permeability is mediated by NRG-1/HER2 signaling through IL-1beta regulation PMID: 26202361
  58. VAMP2-NRG1 is a novel oncogenic fusion gene representing a new addition to the list of NRG1 fusion genes, which together may form an important diagnostic and clinical category of lung adenocarcinoma cases. PMID: 26134228
  59. we carried out the first structural and functional studies on the NRG1 type III cytoplasmic domain. PMID: 25944317
  60. Results suggest a regulatory function of E-cadherin that modulates Nrg1 signaling and promotes Schwann cell myelin formation PMID: 25988855
  61. found no evidence to support the claim that the Nrg1 TM HET mouse represents a simple haploinsufficient model. Further research is required to explore the possibility that mutation results in a gain of Nrg1 function PMID: 25992564
  62. 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 PMID: 26588216
  63. The results indicate that NRG1 promotes progression of gastric cancer by regulating the self-renewal of gastric cancer stem cells and its overexpression is associated with a prognosis of gastric cancer PMID: 25381017
  64. NRG1 is a promising biomarker that can predict response to ERBB3 inhibition by AV-203 in preclinical human cancer models. PMID: 25542901
  65. Genetic risk for Hirschsprung disease in individuals of European ancestry can only be detected at RET (rs2435357 and rs2506030) and at SEMA3 (rs11766001), but not at NRG1. PMID: 25666438
  66. Progression of MS disease could be influenced by variations in NRG1 gene, which might have an impact on remyelination capacity in different patients. PMID: 25802071
  67. Data indicate that high heregulin mRNA and high HER3 protein levels are independently correlated with poor overall survival in patients with oropharyngeal squamous cell carcinoma. PMID: 26195293
  68. neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma PMID: 26269601
  69. Study suggests the involvement of NRG1 in the susceptibility for developing cognitive deficits in schizophrenic patients. PMID: 25967537
  70. these studies support the rationale to target the NRG1-ErbB3-ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas. PMID: 26206558
  71. findings suggest that the neuregulin-1 gene (NRG1) may be involved in the etiological mechanisms of obstructive sleep apnea (OSA) and that carriers of a particular NRG1 mutation may be less likely to have OSA if they do not drink alcoholic beverages PMID: 25325441
  72. NRG1, NF1 and Hippo pathway fusions play important roles in lung cancer. PMID: 25531467
  73. RET and NRG1 variants are common susceptibility factors for HSCR in Indonesia. These common variants demonstrate that development of HSCR requires joint effects of RET and NRG1 early in gut development. PMID: 25475805
  74. rs35753505 and rs6994992 SNPs in NRG1 revealed a statistically significant family-based association with three quantitative traits for sociality. PMID: 25858800
  75. Study showed that NRG1 induces the expression of cancer stem cells-like characteristics in a number of breast cancer cell lines. PMID: 25018110
  76. NRG1beta1 treatment does not increase cardiomyocyte DNA synthesis (and consequently does not increase the rate of cardiomyocyte renewal) in normal or infarcted adult mouse hearts. PMID: 25545368
  77. Results show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. PMID: 25952648
  78. The results of this study suggest that SNP rs35753505 of NRG1 plays an important role in conferring susceptibility to the schizophrenia in a Pakistani population. PMID: 25106628
  79. NRG1 may be a susceptibility gene in psychosis spectrum disorders, particularly BD. PMID: 25244971
  80. identifying neuregulin 1 and its cognate receptor ERBB4 [epidermal growth factor receptor (EGFR) family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4] as a major receptor complex that activates YAP activity PMID: 25492964
  81. These observations connect the unusual nuclear function of a growth factor receptor with a mechanosensory pathway and suggest that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. PMID: 25492965
  82. Phosphorylated ErbB1-4 and heregulin contribute to poorer patient prognosis in CRC. This heregulin-ErbB family member autocrine loop may be a candidate for targeted treatment of CRC. PMID: 25416285
  83. 2 different groups of SNPs were found in NRG1 gene: one showing a nominal association with higher scores of the PANSS-positive dimension and the other one with higher scores of the PANSS-negative dimension. PMID: 25142529
  84. In homozygotes of risk allele (AA) of NRG1, there was a trend to volumetric reductions in brain regions, regardless of schizophrenia diagnosis. PMID: 25042954
  85. Genetic variation in NRG1 is associated with age-related changes on brain development during typical childhood and adolescence. PMID: 24865593
  86. A significant association between circulating levels of neuregulin-1 and paroxysmal non-valvular atrial fibrillation was found. PMID: 24447735
  87. results show that perturbing NRG1 intracellular domain formation has major effects on cell signaling, including inflammatory and neurite formation pathways, and may contribute significantly to schizophrenia pathophysiology PMID: 24380930
  88. Results show that CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous lung adenocarcinomas. PMID: 24469108
  89. results suggest that the 3' region of the NRG1 gene plays a role in BPI susceptibility in the Chinese Han populatio PMID: 24767010
  90. Schizophrenia-risk genotype is associated with lower expression of NRG1-IVNV during the fetal and early neonatal critical period. PMID: 24935406
  91. This study demonistrated that Neuregulin-1 overexpression and Trp53 haploinsufficiency cooperatively promote de novo malignant peripheral nerve sheath tumor pathogenesis. PMID: 24232507
  92. The data of this study suggested that increased NRG1 protein accumulation could contribute to upper motor neuron disease through microglial activation in corticospinal tracts. PMID: 24229388
  93. An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models. PMID: 24044505
  94. The authors' findings suggest a curvilinear association between depression symptom severity and longitudinal patterns of psychotic symptoms that is moderated by NRG1 genotype. PMID: 24123921
  95. NRG1-typeIII+/- transgenic mice exhibit suppressed extracellular signal-regulated kinase activity in myelinated nerves. PMID: 24872569
  96. The study suggests that NRG-1 is a potential new biomarker of OAB; the urothelium might be a therapeutic target for OAB treatment. PMID: 24152577
  97. This review describes the role of neuregulin 1 isoforms in peripheral nerve regeneration and repair. PMID: 24083437
  98. Decreased SLC1A6 expression in an NRG1 risk variant genotype may be an adaptive effect to restore glutamate signalling. PMID: 22424243
  99. Neuregulin 1 expression is reduced in biopsies from patients with neurofibromatosis type 2. PMID: 24309211
  100. Recombinant NRG-1 is a potent inhibitor of doxorubicin-induced cardiac myocyte apoptosis. PMID: 23590603

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Involvement in disease A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.
Subcellular Location Pro-neuregulin-1, membrane-bound isoform: Cell membrane, Single-pass type I membrane protein, Note=Does not seem to be active, SUBCELLULAR LOCATION: Neuregulin-1: Secreted, SUBCELLULAR LOCATION: Isoform 8: Nucleus, Note=May be nuclear, SUBCELLULAR LOCATION: Isoform 9: Secreted, Note=Has a signal peptide, SUBCELLULAR LOCATION: Isoform 10: Membrane, Single-pass type I membrane protein
Protein Families Neuregulin family
Tissue Specificity Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stom
Database Links

HGNC: 7997

OMIM: 142445

KEGG: hsa:3084

STRING: 9606.ENSP00000349275

UniGene: Hs.453951

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