Recombinant Human 4-1BB/TNFRSF9/CD137 Protein

SDS-Page: Human 4-1BB/TNFRSF9/CD137 Protein [NBP2-34958]

• Reactivity: Hu
• Applications: PAGE, Bioactivity
• Format: Carrier-Free
• Concentration: LYOPH

Recombinant Human 4-1BB/TNFRSF9/CD137 Protein Summary

• Description: A single non-glycosylated polypeptide chain containing 166 amino acids corresponding to 4-1BB/TNFRSF9/CD137 Source: E. coli

  Uniprot ID: Q07011

  Amino Acid Sequence: ERTRSLQDPC SNCPAGTFCD NNRNQICSPC PPNSFSSAGG QRTCDICRQC KGVFRTRKEC SSTSNAECDC TPGFHCLGAG CSMCEQDCKQ GQELTKKGCK DCCFGTFNDQ KRGICRPWTN CSLDGKSVLV NGTKERDVVC GPSPADLSPG ASSVTPPAPA REPGHS

• Details of Functionality: CD137 protein is fully biologically active when compared to standard. The biological activity is determined by its inhibitory effect of IL-8 production using human peripheral blood mononuclear cells. About 90 % of inibition was seen using a concentration of 1 ug for both 4-1BB Ligand and 4-1BB Receptor.
• Source: E. coli
• Protein/Peptide Type: Recombinant Protein
• Gene: TNFRSF9
• Purity: > 97 % pure by SDS-PAGE and HPLC
• Endotoxin Note: Less than 1 EU/ug of 4-1BB/TNFRSF9/CD137 as determined by LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
  • SDS-Page
• Theoretical MW: 17.7 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.

Packaging, Storage & Formulations

• Storage: Store at -20 to -70C as supplied. After reconstitution, store at 2 to 8C for 1 month and at -20 to -70C for long term storage. Avoid repeated freeze-thaw cycles.
• Buffer: Lyophilized from a 0.2 um filtered concentrated solution in 10 mM PB, pH 8.0, 150 mM NaCl.
• Preservative: No Preservative
• Concentration: LYOPH
• Purity: > 97 % pure by SDS-PAGE and HPLC
• Reconstitution Instructions: Recommended to centrifuge prior to opening. Reconstitute in sterile distilled water or aqueous buffer containing 0.1% BSA to a concentration of 0.1-1.0mg/mL.

Alternate Names for Recombinant Human 4-1BB/TNFRSF9/CD137 Protein

• 4-1BB ligand receptor
• 41BB
• 4-1BB
• CD137 antigen
• CD137
• CD137MGC2172
• CDw137
• FLJ43501
• ILA
• ILAhomolog of mouse 4-1BB
• induced by lymphocyte activation (ILA)
• interleukin-activated receptor, homolog of mouse Ly63
• receptor protein 4-1BB
• T cell antigen ILA
• T-cell antigen 4-1BB homolog
• T-cell antigen ILA
• TNFRSF9
• tumor necrosis factor receptor superfamily member 9
• tumor necrosis factor receptor superfamily, member 9

Background

4-1BB, also called CD137 and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), is a type I surface glycoprotein expressed on activated T cell and natural killer (NK) cells (1,2). Human 4-1BB protein is 255 amino acids (aa) in length with a theoretical molecular weight of 28 kDa. It contains an extracellular domain, a helical transmembrane domain, and a cytoplasmic/intracellular domain (3). 4-1BB/TNFRSF9/CD137 is a costimulatory receptor that binds the ligand 4-1BBL/CD137L which is primarily expressed on antigen presenting cells (APCs) such as dendritic cells (DCs), macrophages, and B cells (1,2,4,5). The 4-1BB receptor-ligand interaction results in recruitment of TNFR-associated factor (TRAF) family adaptor proteins to 4-1BB's cytoplasmic domain (1,2,4,5). TRAF1, TRAF2, and TRAF3 are found in various homodimer and/or heterodimer configurations. Their recruitment to 4-1BB/CD137 initiates signalosome formation as well as activation of the nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling cascade (1,4,5). 4-1BB/TNFRSF9/CD137 stimulation leads to increased cellular cytotoxic activity and pro-inflammatory cytokine production (1,2,4). Given its role in immune cell activation, 4-1BB has become a promising target for cancer immunotherapy (1,2,4). Current approaches to target 4-1BB include agonistic monoclonal and bispecific anti-4-1BB antibodies and well as utilizing the cytoplasmic domain of 4-1BB in generating chimeric antigen receptors (CARs) (1,2,4). 4-1BB agonists in clinical trials include Urelumab and Utolimumab. Utolimumab also has ligand blocking properties whereas Urelumab does not (1,2,4). Anti-4-1BB monoclonal antibodies are being tested as monotherapy as well as combination therapy with either other immunostimulatory monoclonal antibodies or with checkpoint blockade antibodies like anti-PD-1 (1,2,4).

References

1. Etxeberria, I., Glez-Vaz, J., Teijeira, A., & Melero, I. (2020). New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis. ESMO open, 4(Suppl 3), e000733. https://doi.org/10.1136/esmoopen-2020-000733

2. Chester, C., Sanmamed, M. F., Wang, J., & Melero, I. (2018). Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies. Blood, 131(1), 49-57. https://doi.org/10.1182/blood-2017-06-741041

3. Uniport (Q07011)

4. Chester, C., Ambulkar, S., & Kohrt, H. E. (2016). 4-1BB agonism: adding the accelerator to cancer immunotherapy. Cancer Immunology, Immunotherapy: CII, 65(10), 1243-1248. https://doi.org/10.1007/s00262-016-1829-2

5. Zapata, J. M., Perez-Chacon, G., Carr-Baena, P., Martinez-Forero, I., Azpilikueta, A., Otano, I., & Melero, I. (2018). CD137 (4-1BB) signalosome: complexity is a matter of TRAFs. Frontiers in Immunology, 9, 2618. https://doi.org/10.3389/fimmu.2018.02618

Limitations

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Peptides and proteins are guaranteed for 3 months from date of receipt.

Bioinformatics

• Gene Symbol: TNFRSF9
• Uniprot:
  • Q07011()
  • Q07011()
  • Q07011()