DR4 (death receptor 4), also known as CD261, TRAILR1 and APO-2, is a single pass type 1 transmembrane glycoprotein in the TNF receptor superfamily (TNFRSF10A). DR4 contains an extracellular region with 3 cysteine-rich repeats and a cytoplasmic death domain (DD). DR4 is widely expressed with high levels in spleen, peripheral blood leukocytes, small intestine and thymus. DR4 is detected mainly in damaged, infected and malignant cells.  DR4 is also expressed on hemopoietic cells including activated T-cells and influences activities such as monocyte migration. DR4 is one of 5 receptors for TRAIL (tumor necrosis factor-related apoptosis inducing ligand), also known as Apo2L (Apo-2 ligand) and TNFSF10.  TRAIL preferentially induces apoptosis in tumor cell lines, but not in normal cells. TRAIL binds at least 5 different receptors with characteristic TNFR cysteine-rich repeats. DR4/TRAILR1 is most closely related to DR5/TRAILR2 sharing 59% amino acid identity within the cytoplasmic DD. DR4 transduces cell death signal and induces apoptosis by recruiting a cytosolic death­inducing signaling complex (DISC) that includes the adaptor FADD and caspase 8 and caspase 10. DR4 is thought to function in immune surveillance, inducing apoptosis in cancer cells but not normal cells. DR4 surface expression correlates more closely than that of DR5 with TRAIL induction of apoptosis in tumor cells.

DR4 (death receptor 4), also known as CD261, TRAILR1 and APO-2, is a single pass type 1 transmembrane glycoprotein in the TNF receptor superfamily (TNFRSF10A). DR4 contains an extracellular region with 3 cysteine-rich repeats and a cytoplasmic death domain (DD). DR4 is widely expressed with high levels in spleen, peripheral blood leukocytes, small intestine and thymus. DR4 is detected mainly in damaged, infected and malignant cells.  DR4 is also expressed on hemopoietic cells including activated T-cells and influences activities such as monocyte migration. DR4 is one of 5 receptors for TRAIL (tumor necrosis factor-related apoptosis inducing ligand), also known as Apo2L (Apo-2 ligand) and TNFSF10.  TRAIL preferentially induces apoptosis in tumor cell lines, but not in normal cells. TRAIL binds at least 5 different receptors with characteristic TNFR cysteine-rich repeats. DR4/TRAILR1 is most closely related to DR5/TRAILR2 sharing 59% amino acid identity within the cytoplasmic DD. DR4 transduces cell death signal and induces apoptosis by recruiting a cytosolic death­inducing signaling complex (DISC) that includes the adaptor FADD and caspase 8 and caspase 10. DR4 is thought to function in immune surveillance, inducing apoptosis in cancer cells but not normal cells. DR4 surface expression correlates more closely than that of DR5 with TRAIL induction of apoptosis in tumor cells.

  

Product Details

 

Gene Symbol: TNFRSF10A; APO2; CD261; TRAILR1; TRAIL-R1; TRAILR-1

  

NCBI Gene ID: 8797

 

Uniprot Entry: O00220

 

Construct Details: The recombinant human DR4-Fc fusion is expressed as a 445 amino acid protein consisting of Ala24 - Asn239 region of DR4 (UniProt accession #O00220) and a C-terminal Fc from human IgG1, which exists as a dimer under non-reducing conditions (see the gel image inserted above).  

   

Source: Human cells stably expressing human DR4-Fc and growing in chemical-defined media with no animal components or antibiotics

 

Deduced Amino Acid Sequence: 

        10         20         30         40         50         60 

ASGTEAAAAT PSKVWGSSAG RIEPRGGGRG ALPTSMGQHG PSARARAGRA PGPRPAREAS 

        70         80         90        100        110        120 

PRLRVHKTFK FVVVGVLLQV VPSSAATIKL HDQSIGTQQW EHSPLGELCP PGSHRSEHPG 

       130        140        150        160        170        180 

ACNRCTEGVG YTNASNNLFA CLPCTACKSD EEERSPCTTT RNTACQCKPG TFRNDNSAEM 

       190        200        210        220        230        240 

CRKCSRGCPR GMVKVKDCTP WSDIECVHKE SGNGHNGSTG THTCPPCPAP ELLGGPSVFL 

       250        260        270        280        290        300 

FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV EVHNAKTKPR EEQYNSTYRV 

       310        320        330        340        350        360 

VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ PREPQVYTLP PSREEMTKNQ 

       370        380        390        400        410        420 

VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSKLTV DKSRWQQGNV 

       430        440 

FSCSVMHEAL HNHYTQKSLS LSPGK 

 

M.W.: Calculated molecular mass (kDa): 48.5; Estimated by SDS-PAGE under reducing condition (kDa): 50-55

 

Calculated PI: 8.74

 

Calculated extinction coefficients (M-1 cm-1, at 280nm): 54650

 

Purity: >95% judged by SDS-PAGE under reducing condition (see the gel image above, labeled as "DTT: +")

 

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

 

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

 

Biological Activity: Binds to its ligand human TRAIL and inhibits TRAIL-mediated signaling activity including TRAIL-­induced cytotoxicity in L-929 mouse fibroblast 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. Science 276:111 (1997).

2. J. Immunol. 175:1232 (2005).

3. Mol. Cancer Ther. 6:2591 (2007).

4. Clin. Cancer Res. 15:5584 (2009).

5. Oncogene 29:4848 (2010).

 

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here: FCLSF54-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.