Recombinant Human HB-EGF Protein

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Product Details

Summary
Reactivity HuSpecies Glossary
Applications Bioactivity

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Recombinant Human HB-EGF Protein Summary

Details of Functionality
Measured in a cell proliferation assay using Balb/3T3 mouse embryonic fibroblast cells. Rubin, J.S. et al. (1991) Proc. Natl. Acad. Sci. USA 88:415. The ED50 for this effect is 0.15-0.75 ng/mL.
Source
Spodoptera frugiperda, Sf 21 (baculovirus)-derived human HB-EGF protein
Asp63-Leu148
Accession #
N-terminal Sequence
Asp63 (major), Gly32, Glu24
Protein/Peptide Type
Recombinant Proteins
Gene
HBEGF
Purity
>97%, by SDS-PAGE with silver staining
Endotoxin Note
<1.0 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

Theoretical MW
9.7 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
11-20 kDa, reducing conditions
Publications
Read Publications using
259-HE in the following applications:

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 BSA as a carrier protein.
Purity
>97%, by SDS-PAGE with silver staining
Reconstitution Instructions
Reconstitute at 250 μg/mL in sterile PBS containing at least 0.1% human or bovine serum albumin.

Notes

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

Alternate Names for Recombinant Human HB-EGF Protein

  • diphtheria toxin receptor (heparin-binding epidermal growth factor-like growthfactor)
  • Dtr
  • DTRHEGFLdiphtheria toxin receptor (heparin-binding EGF-like growth factor)
  • Dts
  • DTSF
  • HBEGF
  • HB-EGF
  • Hegfl
  • heparin-binding EGF-like growth factor
  • heparin-binding epidermal growth factor
  • proheparin-binding EGF-like growth factor

Background

Human HB-EGF (Heparin-Binding EGF-like growth factor) is a 12-16 kDa member of the EGF family of peptide growth factors (1-3). Also known as the DTR (diphtheria toxin receptor), it is further classified as a group 2 ErbB ligand based on its ability to activate both the EGF/ErbB1 and ErbB4 receptors (4, 5). HB-EGF is synthesized as a 208 amino acid (aa) type I transmembrane preproprecursor (1, 6). It contains a 19 aa signal sequence, a 43 aa prosegment, an 86 aa mature region (aa 63-148), an 11 aa juxtamembrane cleavage peptide, a 24 aa transmembrane segment, and a 25 aa cytoplasmic tail (aa 184-208). As an integral membrane protein, HB-EGF is expressed as a 19-27 kDa protein in mammalian cells (7-9). The variability in molecular weight (MW) is attributed to heterogeneity in glycosylation and/or the utilization of multiple proteolytic cleavage sites during maturation. Mature HB-EGF is a soluble peptide that arises from proteolytic processing of the transmembrane form. It possesses an EGF-like domain between aa 104-144, and a heparin-binding motif between aa 93‑113. Although the aa range for "mature" HB-EGF is typically stated to be Asp63-Leu148, potential N-terminal start (cleavage) sites also exist at Gly32, Arg73, Val74, Ser77 and Ala82 (8, 10-12). Thus, differential processing (in part) likely accounts for the 16-23 kDa range in MW noted for mammalian-derived mature HB-EGF. Proteases suggested to contribute to HB-EGF processing include TACE, MMP-3 and -7, ADAM-17 and ADAM-12 (11, 13-16). When expressed recombinantly in E.coli, HB-EGF (aa 73-148) runs at 14 kDa in SDS-PAGE; when expressed in Baculovirus, HB-EGF (aa 63-148, 77-148 and 32-148) runs at 18 kDa, 15 kDa, and 19 kDa respectively (8, 12, 17). Over aa 63-148, human HB-EGF- shares 76% and 73% aa sequence identity with rat and mouse HB-EGF, respectively (1, 18). Cells known to express HB-EGF include bronchial epithelium (19), visceral and vascular smooth muscle (20, 21), CD4+ T cells (22), cardiac muscle (23), glomerular podocytes (24), keratinocytes (13) and IL-10-secreting regulatory macrophages (25). As noted earlier, HB-EGF is known to bind to both 170 kDa EGFR and 180 kDa ErbB4, and through heterodimerization, ErbB2 (13, 26). Activity associated with ErbB4 binding appears to be limited to non-mitogenic actions, while EGFR binding induces both mitogenic and non-mitogenic activity.
  1. Higashiyama, S et al. (1991) Science 251:936.
  2. Schneider, MR & E. Wolf (2009) J. Cell. Physiol. 218:460.
  3. G.V. Sherbet (2011) The Epidermal Growth Factor (EGF) Family in Growth Factors and Their Receptors in Cell Differentiation, Cancer and Cancer Therapy, Pages 173-198. Elsevier, NY.
  4. Iwamoto, R & E. Mekada (2000) Cytokine Growth Factor Rev. 11:335.
  5. Miyata, K. et al. (2012) Anticancer Res. 32:2347.
  6. SwissProt:Q99075.
  7. Raab, G. et al. (1994) Biochem. Biophys. Res. Commun. 204:592.
  8. Nakagawa, T. et al. (1996) J. Biol. Chem. 271:30858.
  9. Higashiyama, S. et al. (1995) J. Cell Biol. 128:929.
  10. Higashiyama, S. et al. (1992) J. Biol. Chem. 267:6205.
  11. Hinkle, C.L. et al. (2004) J. Biol. Chem. 279:24179.
  12. Ono, M. et al. (1994) J. Biol. Chem. 269:31315.
  13. Nanba, D. & S. Higashiyama (2004) Cytokine Growth Factor Rev. 15:13.
  14. Cheng, K. et al. (2007) Biochem. Pharmacol. 73:1001.
  15. Suzuki, M. et al. (1997) J. Biol. Chem. 272:31730.
  16. Asakura, M. et al. (2002) Nat. Med. 8:35.
  17. Marikovsky, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90:3889.
  18. Abraham, J.A. et al. (1993) Biochem. Biophys. Res. Commun. 190:125.
  19. Tschumperlin, D.J. et al. (2004) Nature 429:83.
  20. Park, J.M. et al. (1998) Am. J. Physiol. 275:C1247.
  21. Miyagawa, J. et al. (1995) J. Clin. Invest. 95:404.
  22. Blotnick, S. et al. (1994) Proc. Natl. Acad. Sci. USA 91:2890.
  23. Iwamoto, R. et al. (2003) Proc. Natl. Acad. Sci. USA 100:3221.
  24. Bollee, G. et al. (2011) Nat. Med. 17:1242.
  25. Edwards, J.P. et al. (2009) J. Immunol. 182:1929.
  26. Elenius, K. et al. (1997) EMBO J. 16:1268.

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259-HE
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Applications: Bioactivity

Publications for HB-EGF (259-HE)(45)

We have publications tested in 5 confirmed species: Human, Mouse, Fish - Prionace glauca (blue shark), N/A, Zebrafish.

We have publications tested in 4 applications: Bioassay, ELISA Standard, In Vivo, In vivo injection.


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Bioassay
(34)
ELISA Standard
(1)
In Vivo
(6)
In vivo injection
(1)
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Human
(23)
Mouse
(16)
Fish - Prionace glauca (blue shark)
(1)
N/A
(1)
Zebrafish
(2)
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Showing Publications 1 - 10 of 45. Show All 45 Publications.
Publications using 259-HE Applications Species
A Farinazzo, S Angiari, E Turano, E Bistaffa, S Dusi, S Ruggieri, R Bonafede, R Mariotti, G Constantin, B Bonetti Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis Sci Rep, 2018;8(1):7473. 2018 [PMID: 29748664] (Bioassay, Mouse) Bioassay Mouse
T Lai, Y Li, M Chen, G Pan, X Wen, Z Mai, Y Yuan, Y Lv, Q Lv, R Cen, H Yi, M Wen, D Li, B Wu, D Wu, C Cao Heparin-binding epidermal growth factor contributes to COPD disease severity by modulating airway fibrosis and pulmonary epithelial-mesenchymal transition Lab. Invest., 2018;0(0):. 2018 [PMID: 29581578] (Bioassay, Human) Bioassay Human
S Zambrano, PQ Rodriguez, J Guo, K Möller-Hac, A Schwarz, J Patrakka FYVE domain-containing protein ZFYVE28 regulates EGFR-signaling in podocytes but is not critical for the function of filtration barrier in mice Sci Rep, 2018;8(1):4712. 2018 [PMID: 29549365] (Bioassay, Human) Bioassay Human
F Elsaeidi, P Macpherson, EA Mills, J Jui, JG Flannery, D Goldman Notch suppression collaborates with Ascl1 and Lin28 to unleash a regenerative response in fish retina, but not in mice J. Neurosci., 2018;0(0):. 2018 [PMID: 29378863] (In Vivo, Zebrafish) In Vivo Zebrafish
T Tanaka, Y Zhou, T Ozawa, R Okizono, A Banba, T Yamamura, E Oga, A Muraguchi, H Sakurai Ligand-activated epidermal growth factor receptor (EGFR) signaling governs endocytic trafficking of unliganded receptor monomers by non-canonical phosphorylation J. Biol. Chem., 2017;0(0):. 2017 [PMID: 29255092]
S Kim, L Yang, S Kim, RG Lee, MJ Graham, JA Berliner, AJ Lusis, L Cai, RE Temel, DL Rateri, S Lee Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development PLoS ONE, 2017;12(8):e0182566. 2017 [PMID: 28792970] (In Vivo, Mouse) In Vivo Mouse
T Venkataram, C Coleman, M Frieman Overactive EGFR Signaling Leads to Increased Fibrosis After SARS-CoV Infection J. Virol., 2017;0(0):. 2017 [PMID: 28404843] (In Vivo, Mouse) In Vivo Mouse
K Kizawa, T Fujimori, T Kawai Arachidonate 12-Lipoxygenase Inhibitors Promote S100A3 Citrullination in Cultured SW480 Cells and Isolated Hair Follicles Biol. Pharm. Bull., 2017;40(4):516-523. 2017 [PMID: 28381806] (Bioassay, Human) Bioassay Human
R Iwamoto, N Mine, H Mizushima, E Mekada ErbB1 and ErbB4 generate opposing signals regulating mesenchymal cell proliferation during valvulogenesis J. Cell. Sci, 2017;0(0):. 2017 [PMID: 28232522] (Bioassay, Human) Bioassay Human
Molecular Characterization of Striated Muscle-Specific Gab1 Isoform as a Critical Signal Transducer for Neuregulin-1/ErbB Signaling in Cardiomyocytes PLoS ONE, 2016;11(11):e0166710. 2016 [PMID: 27861634] (In Vivo, Mouse) In Vivo Mouse
Show All 45 Publications.

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Bioinformatics

Gene Symbol HBEGF
Entrez
Uniprot