SIGIRR (single immunoglobulin IL-1 receptor-related molecule) is a single-pass type III membrane protein that belongs to the interleukin 1 receptor (IL1R) family. The IL1R family comprises at least 10 members, which typically contain 3 immunoglobulin (Ig)-like domains in the extracellular region and an intracellular TIR (Toll-like receptor/IL-1 receptor) signaling domain that is also conserved in the Toll-like receptor family. Although SIGIRR contains the conserved Ig-like and TOR motifs, it differs from the other 9 members by having only one Ig-like domain. Human SIGIRR lacks signal peptide and contains a cytoplasmic extention beyond the TIR domain, which is reminiscent of the structure of Toll and Toll­like receptor family members but absent in most IL­1 receptor family members. SIGIRR is widely expressed in mouse and human epithelial tissues, such as kidney, lung and gut. The ligand and signaling mechanism for SIGIRR remain unclear. SIGIRR may act as a negative regulator for Toll-IL-1R signaling by trapping the crucial components of the pathway. Inflammation is enhanced in SIGIRR-deficient mice, as demonstrated by the increased chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. SIGIRR may plays critical role in gut homeostasis, intestinal inflammation, and colitis-associated tumorigenesis by maintaining the microbial tolerance of the colonic epithelium. Moreover, SIGIRR-deficient mice developed stronger Th2 immune response, suggesting that SIGIRR is an important regulator of Th2, possibly through its impact on IL-33-mediated signaling pathway.

SIGIRR (single immunoglobulin IL-1 receptor-related molecule) is a single-pass type III membrane protein that belongs to the interleukin 1 receptor (IL1R) family. The IL1R family comprises at least 10 members, which typically contain 3 immunoglobulin (Ig)-like domains in the extracellular region and an intracellular TIR (Toll-like receptor/IL-1 receptor) signaling domain that is also conserved in the Toll-like receptor family. Although SIGIRR contains the conserved Ig-like and TOR motifs, it differs from the other 9 members by having only one Ig-like domain. Human SIGIRR lacks signal peptide and contains a cytoplasmic extention beyond the TIR domain, which is reminiscent of the structure of Toll and Toll­like receptor family members but absent in most IL­1 receptor family members. SIGIRR is widely expressed in mouse and human epithelial tissues, such as kidney, lung and gut. The ligand and signaling mechanism for SIGIRR remain unclear. SIGIRR may act as a negative regulator for Toll-IL-1R signaling by trapping the crucial components of the pathway. Inflammation is enhanced in SIGIRR-deficient mice, as demonstrated by the increased chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. SIGIRR may plays critical role in gut homeostasis, intestinal inflammation, and colitis-associated tumorigenesis by maintaining the microbial tolerance of the colonic epithelium. Moreover, SIGIRR-deficient mice developed stronger Th2 immune response, suggesting that SIGIRR is an important regulator of Th2, possibly through its impact on IL-33-mediated signaling pathway.

 

Product Details

 

Gene Symbol: SIGIRR

 

NCBI Gene ID: 59307

 

Uniprot Entry: Q6IA17

 

Construct Details: The recombinant human SIGIRR ECD is expressed as a 357 amino acid protein consisting of Met1 ­His118 region of SIGIRR (UniProt accession #Q6IA17) and a C-terminal Fc from human IgG1, which exists as a dimer under non-reducing conditions.  

 

Source: Human cells stably expressing human IL1RAP-Fc and growing in chemical-defined media with no animal components or antibiotics

 

Deduced Amino Acid Sequence:

MPGVCDRAPDFLSPSEDQVLRPALGSSVALNCTAWVVSGPHCSLPSVQWLKDGLPLGIGGHYSLHEYSWVK

ANLSEVLVSSVLGVNVTSTEVYGAFTCSIQNISFSSFTLQRAGPTSHGSTTENLYFQGSTGTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

 

M.W.: Calculated molecular mass (kDa): 39.3; Estimated by SDS-PAGE under reducing condition (kDa): ~55 (probably due to glycosylation).

 

Calculated PI: 6.26

 

Calculated extinction coefficients (M-1 cm-1, at 280nm):  57870

 

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 PBSpH7.4 (carrier & preservative free). The purified recombinant protein was labeled with Biotin (3-5 Biotin per molecule) using the standard procedure.

 

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

 

Biological Activity: Not available.

 

  

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. Cytokine 11: 389-399 (1999).

2. Nat. Immunol. 4:920-927 (2003).

3. J. Biol. Chem. 280:25233-25241 (2005).

4. Immunity . 26: 461-475 (2007).

5. J Immunol. 182: 2601-2609 (2009).

 

 

 

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here: FCL1308B-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.