SIGIRR
| SIGIRR | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 11: 0.41 – 0.42 Mb | Chr 7: 140.67 – 140.68 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate
Gene
Human gene SIGIRR is localized on chromosome 11. It is composed of 10 exons spanning about 11,700 base pairs.[6] In mice, this gene is on chromosome 7, where it is composed of 9 exons spanning about 9,400 base pairs.[7]
Structure
SIGIRR is a 410
Expression
SIGIRR is expressed in several epithelial tissues, particularly in epithelial cells of kidneys, digestive tract, liver, lungs, and in lymphoid organs.[6] It is also expressed in monocytes, B lymphocytes, T lymphocytes, dendritic cells, and NK cells. In general, its expression is downregulated during inflammation or infection.[5] Its reduced expression was also found in patients with chronic lymphoid leukemia,[9] or in cells from colonic cancer. In human cells from colonic cancer, it was observed that there was an increased expression of one variant of SIGIRR. This variant lacks its exon 8, is not glycosylated and its function is impaired. It also inhibits glycosylation of the Wild type variant as its transported to the plasmatic membrane.[8]
One of the discovered
Function
SIGIRR negatively regulates the activation of the IL-1R1,
SIGIRR interacts with IL-1R1 when it binds to IL-1. N terminal extracellular
Negative regulation of
SIGIRR as a coreceptor of IL-1R5 for IL-37 binding
SIGIRR takes part in mediating the anti-inflammatory IL-37 signalization. It interacts with IL-37, IL-18R1 and forms tripartite signaling complex. Activity of this complex transduce anti-inflammatory signal and is essential for manifestation of IL-37 activity. Upon this signalization it causes inhibition of components of NF-κB pathway, kinases mTOR, TAK1, FYN, p38, JNK, ERK and it also causes activation of phosphatase PTEN, kinase MER, transcription factor STAT3 and adaptor protein p62 (DOK1). Pre-treatment of mice by IL-37 before injection of lipopolysaccharide reduced examined levels of pro-inflammatory cytokines and, also reduced their weight loss and hypothermia. This protective effect of IL-37 was abolished by deletion of SIGIRR, reduction of its expression or neutralization of IL-37 by antibodies.[18][19]
In addition to the regulation of inflammation, IL-37 also affects metabolism. Stimulation of skeletal muscle cells by IL-37 increases level of AMP-dependent kinase, increases its activation and induces metabolic reprogramming. It causes increase of oxidative phosphorylation, Krebs cycle, nucleotide, amino acids metabolism, and decrease of inflammatory mediators levels. This response does not occur in case of SIGIRR deficiency[20]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000185187 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025494 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 29247989.
- ^ PMID 10346978.
- ^ "Sigirr single immunoglobulin and toll-interleukin 1 receptor (TIR) domain [Mus musculus (house mouse)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-01-24.
- ^ PMID 26344057.
- S2CID 11804905.
- ^ PMID 21077278.
- PMID 24821721.
- ^ PMID 15866876.
- ^ S2CID 25246605.
- ^ PMID 26276688.
- PMID 20025973.
- PMID 20060329.
- PMID 20416302.
- S2CID 24578661.
- PMID 25654981.
- PMID 28193888.
Further reading
- Du X, Poltorak A, Wei Y, Beutler B (September 2000). "Three novel mammalian toll-like receptors: gene structure, expression, and evolution". European Cytokine Network. 11 (3): 362–71. PMID 11022119.
- Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, et al. (October 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research. 13 (10): 2265–70. PMID 12975309.
- Polentarutti N, Rol GP, Muzio M, Bosisio D, Camnasio M, Riva F, et al. (2004). "Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR". European Cytokine Network. 14 (4): 211–8. PMID 14715412.
- Qin J, Qian Y, Yao J, Grace C, Li X (July 2005). "SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms". The Journal of Biological Chemistry. 280 (26): 25233–41. PMID 15866876.