HER4 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK).  Four members of the EGFR family have been identified: EGFR (ERBB1, HER1), HER2 (ERBB2), HER3 (ERBB3) and HER4 (ERBB4).  They typically contain an extracellular ligand binding domain (ECD), a transmembrane domain (TM), and an intracellular kinase domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity.  EGFR signaling is initiated by ligand binding to the extracellular ligand binding domain. This initiates receptor homo-/hetero-dimerization and autophosphorylation by the intracellular kinase domain, resulting in receptor activation. Following activation, phosphorylation of cytoplasmic substrates occurs and a signaling cascade is initiated that drives many cellular responses, including changes in gene expression, cytoskeletal rearrangement, anti-apoptosis and increased cell proliferation.  HER4 ligands include the neuregulins (NRGs), β-cellulin and heparin-binding EGF-like growth factor (HB-EGF). The ligand binding induces a variety of cellular responses including mitogenesis and differentiation.  Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. HER4 and its ligand NRG1 are also implicated in the pathophysiology of schizophrenia.

HER4 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK).  Four members of the EGFR family have been identified: EGFR (ERBB1, HER1), HER2 (ERBB2), HER3 (ERBB3) and HER4 (ERBB4).  They typically contain an extracellular ligand binding domain (ECD), a transmembrane domain (TM), and an intracellular kinase domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity.  EGFR signaling is initiated by ligand binding to the extracellular ligand binding domain. This initiates receptor homo-/hetero-dimerization and autophosphorylation by the intracellular kinase domain, resulting in receptor activation. Following activation, phosphorylation of cytoplasmic substrates occurs and a signaling cascade is initiated that drives many cellular responses, including changes in gene expression, cytoskeletal rearrangement, anti-apoptosis and increased cell proliferation.  HER4 ligands include the neuregulins (NRGs), β-cellulin and heparin-binding EGF-like growth factor (HB-EGF). The ligand binding induces a variety of cellular responses including mitogenesis and differentiation.  Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. HER4 and its ligand NRG1 are also implicated in the pathophysiology of schizophrenia.

 

Product Details

 

Gene Symbol: HER4; ERBB4; HER-4; p180erbB4; p180-erbB4

 

NCBI Gene ID: 2066 (human)

 

Uniprot Entry: Q15303 (human)

 

Construct Details: The recombinant human HER4 extracellular or ecto-domain (ECD) is expressed as a  862 amino acid protein consisting of Gln26-Pro651 region of HER4 and a C-terminal Fc from human IgG1, which exists as a dimmerr under non-reducing conditions.

 

Source: Human cells stably expressing human HER4-Fc and growing in chemical-defined media with no animal components or antibiotics

 

Deduced Amino Acid Sequence:

QSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQ

FRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTI

HWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDC

CHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNF

VVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGN

LIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLS

LLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRKAENCTAEGM

VCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYDGEFREFENGSICVECDPQCEKMEDGLLTC

HGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYP

WTGHSTLPQHARTPSTGDEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

 

M.W.: Calculated molecular mass (kDa): 96.3; Estimated by SDS-PAGE under reducing condition (kDa): 100

 

Calculated PI: 6.14

 

Calculated extinction coefficients (M-1 cm-1, at 280nm):  113170

 

Purity: >95% judged by SDS-PAGE under reducing condition (see the gel image above)

 

Formulation: Supplied at 0.5 mg/ml in sterile PBS pH7.4 (carrier free).

 

Endotoxin Level: <0.1 EU per 1 μg of purified recombinant protein determined by the LAL method

 

Biological Activity:  It was reported to inhibit the biological activity of Neuregulin-1 on MCF‑7 human breast cancer cells

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.

 

Storage

 

The product is shipped at 4°C. Upon receipt, centrifuge the product briefly before opening the vial. It is recommended to store small aliquots at the temperature below –20°C for long-term storage and the product is stable for 3 months. The undiluted protein can be stored at 4°C for no more than 2 weeks.

 

 

Use a manual defrost freezer and avoid repeated freeze-thaw cycles.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

References

 

1. Cancer Research 48:4083, 1988
2. Nature 378: 390-394, 1995
3. Nature Genet. 41: 1127-1132, 2009
4. Nature Med. 12: 824-828, 2006

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here: FCL0139-PDS.pdf

 

 

 

Additional supporting documents, including COA and MSDS are available upon request.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.