Recombinant Human NRG1/HRG1-alpha EGF domain Fc Protein, CF

Recombinant Human NRG1/HRG1-alpha EGF domain Fc Chimera Protein (Catalog # 11343-NR) stimulates proliferation of MCF 7 human breast cancer cells. The ED50 for this effect is 4.00-40.0 ng/mL.

2 μg/lane of Recombinant Human NRG1/HRG1-alpha EGF domain Fc Chimera Protein (Catalog # 11343-NR) was resolved with SDS-PAGE under reducing (R) and non-reducing (NR) conditions and visualized by Coomassie® Blue staining, showing bands at 36-43 kDa and 72-86 kDa, respectively.

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human NRG1/HRG1-alpha EGF domain Fc Protein, CF Summary

• Additional Information: Fc Chimera
• Details of Functionality: Measured in a serum-free cell proliferation assay using MCF‑7 human breast cancer cells. Karey, K.P. et al. (1988) Cancer Research 48:4083. The ED₅₀ for this effect is 4.00‑40.0 ng/mL.
• Source: Human embryonic kidney cell, HEK293-derived human Neuregulin-1/NRG1 protein
  

  Human NRG1/HRG1-alpha EGF domain (Ser177-Pro226) Accession # NP_039254.1	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #: NP_039254.1
• N-terminal Sequence: Ser177
• Structure / Form: Disulfide-linked homodimer
• Protein/Peptide Type: Recombinant Proteins
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 32 kDa.
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 36-43 kDa, under reducing conditions.

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose.
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 500 μg/mL in PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human NRG1/HRG1-alpha EGF domain Fc Protein, CF

• ARIA
• GGF2
• GGFglial growth factor
• Heregulin-1
• HGL
• HGLneu differentiation factor
• HRG
• HRG1
• HRG1-alpha
• HRG1-beta 1
• HRGAneuregulin 1 type IV beta 1a
• MST131
• MSTP131
• NDFheregulin, alpha (45kD, ERBB2 p185-activator)
• neuregulin 1 type IV beta 3
• neuregulin 1
• Neuregulin1
• Neuregulin-1
• NRG1
• pro-neuregulin-1, membrane-bound isoform
• pro-NRG1
• sensory and motor neuron derived factor
• SMDF

Background

Neuregulin-1 (NRG1) belongs to a family of structurally related glycoproteins encoded by four distinct but related genes, Nrg1, Nrg2, Nrg3, and Nrg4. Through alternative splicing or the use of alternative promoters, Nrg1 encodes more than 14 soluble or transmembrane proteins. Type I NRG1 isoforms include Neu Differentiation Factor, Heregulin, and ARIA. These consist of an N-terminal domain, an Ig-like domain, a linker with a Ser/Thr rich region, an EGF-like domain, a transmembrane segment, and a cytoplasmic domain. Type II isoforms such as Glial Growth Factor have a larger N-terminal domain and lack the Ser/Thr rich linker. Type III isoforms such as Sensory and Motor neuron-Derived Factor lack the Ig-like domain but contain a cysteine rich domain (CRD) and a second transmembrane segment (1-5). The alpha and beta splice variants of NRG1 differ in their extracellular juxtamembrane regions (3, 6). This recombinant protein corresponds to the alpha isoforms  NRG1 isoforms exhibit distinct expression patterns and functions (7). The EGF-like domain, which is common to all NRG1 isoforms, is required for Neuregulin binding to ErbB3 or ErbB4 receptors (3). ErbB3 or ErbB4 subsequently heterodimerize with ErbB2, resulting in tyrosine phosphorylation and NRG1 induced signaling (1, 2). Soluble growth factors can be released by TACE/ADAM17, BACE, or ADAM19 mediated shedding of the ECD of transmembrane NRG1 (8 - 10). The cytoplasmic region can be cleaved by gamma -secretase, generating a repressor that inhibits the transcription of proapoptotic genes (11). NRG1 regulates multiple nervous system functions including axon guidance, synapse formation and plasticity, glial cell development, and axon myelination (1, 2). In the heart, NRG1 regulates organ morphogenesis and contractility and also plays a cardioprotective role following tissue injury (12). Multiple polymorphisms and aberrant expression of NRG1 isoforms are associated with the development of schizophrenia and many cancers (1, 2, 13). Fusing Fc tag to NRG1 is reported to extend its half life in circulation and improved signal potency (14).

1. Mei, L. and W.-C. Xiong (2008) Nat. Rev. Neurosci. 9:437.
2. Talmage, D.A. (2008) Novartis Found. Symp. 289:74.
3. Holmes, W.E. et al. (1992) Science 256:1205.
4. Marchionni, M.A. et al. (1993) Nature 362:312.
5. Ho, W.-H. et al. (1995) J. Biol. Chem. 270:14523.
6. Wen, D. et al. (1994) Mol. Cell. Biol. 14:1909.
7. Meyer, D. et al. (1997) Development 124:3575.
8. Hu, X. et al. (2006) Nat. Neurosci. 9:1520.
9. Willem, M. et al. (2006) Science 314:664.
10. Yokozeki, T. et al. (2007) Genes Cells 12:329.
11. Bao, J. et al. (2003) J. Cell Biol. 161:1133.
12. Lemmens, K. et al. (2007) Circulation 116:954.
13. Breleux, M. (2007) Cell. Mol. Life Sci. 64:2358.
14. Zhang, P. et al. (2018) JCI Insight. 3:e98522.

Bioinformatics

• Uniprot:
  • NP_039254.1()