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target has curated data in GtoImmuPdb
Target id: 2969
Nomenclature: single Ig and TIR domain containing
Systematic Nomenclature: IL-1R8
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 1 | 410 | 11p15.5 | SIGIRR | single Ig and TIR domain containing | 8 |
| Mouse | 1 | 409 | 7 F5 | Sigirr | single immunoglobulin and toll-interleukin 1 receptor (TIR) domain | |
| Rat | 1 | 409 | 1q41 | Sigirr | single Ig and TIR domain containing | |
| Previous and Unofficial Names |
| single immunoglobulin and toll-interleukin 1 receptor (TIR) domain | single immunoglobulin domain IL1R1 related | TIR8 |
| Database Links |
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| Alphafold | Q6IA17 (Hs), Q9JLZ8 (Mm), Q4V892 (Rn) |
| Ensembl Gene | ENSG00000185187 (Hs), ENSMUSG00000025494 (Mm), ENSRNOG00000015593 (Rn) |
| Entrez Gene | 59307 (Hs), 24058 (Mm), 309106 (Rn) |
| Human Protein Atlas | ENSG00000185187 (Hs) |
| KEGG Gene | hsa:59307 (Hs), mmu:24058 (Mm), rno:309106 (Rn) |
| OMIM | 605478 (Hs) |
| Pharos | Q6IA17 (Hs) |
| RefSeq Nucleotide | NM_001135054 (Hs), NM_023059 (Mm), NM_001024887 (Rn) |
| RefSeq Protein | NP_001128526 (Hs), NP_075546 (Mm), NP_001020058 (Rn) |
| UniProtKB | Q6IA17 (Hs), Q9JLZ8 (Mm), Q4V892 (Rn) |
| Wikipedia | SIGIRR (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Immunopharmacology Comments |
| IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [5]. |
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| General Comments |
| The SIGIRR protein product, IL-1R8, is a member of the interleukin 1 receptor (IL-1R) superfamily [8]. It contains certain domain motifs that are conserved with other IL-1R proteins, but also has unique features. It has an intracellular Toll-IL-1R (TIR) domain, and has only one Ig domain in its extracellular domain, compared to the three common to other IL-1R family members, and also has a longer cytoplasmic domain than its other related proteins. IL-1R8 appears to act as a decoy receptor that inhibits canonical, proinflammatory IL-1 signalling, by binding signalling proteins IRAK and TRAF6 via interaction with its intracellular TIR domain [7,9]. IL-1R8 has been shown to be an essential component of the functional receptor (IL-1R8/IL-18R1) for the anti-inflammatory cytokine IL-37 [6]. |
1. Bekker LG, Moreira AL, Bergtold A, Freeman S, Ryffel B, Kaplan G. (2000) Immunopathologic effects of tumor necrosis factor alpha in murine mycobacterial infection are dose dependent. Infect Immun, 68 (12): 6954-61. [PMID:11083819]
2. Bulut Y, Faure E, Thomas L, Equils O, Arditi M. (2001) Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol, 167 (2): 987-94. [PMID:11441107]
3. Garlanda C, Di Liberto D, Vecchi A, La Manna MP, Buracchi C, Caccamo N, Salerno A, Dieli F, Mantovani A. (2007) Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by Toll IL-1 receptor 8/single Ig IL-1-related receptor, a negative regulator of IL-1/TLR signaling. J Immunol, 179 (5): 3119-25. [PMID:17709526]
4. Garlanda C, Riva F, Polentarutti N, Buracchi C, Sironi M, De Bortoli M, Muzio M, Bergottini R, Scanziani E, Vecchi A et al.. (2004) Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci USA, 101 (10): 3522-6. [PMID:14993616]
5. Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popović B, Bernardini G, Magrini E, Gianni F et al.. (2017) IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity. Nature, 551 (7678): 110-114. [PMID:29072292]
6. Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, Lotz-Havla AS, Gersting SW, Cho SX, Lao JC et al.. (2015) IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol, 16 (4): 354-65. [PMID:25729923]
7. Qin J, Qian Y, Yao J, Grace C, Li X. (2005) SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem, 280 (26): 25233-41. [PMID:15866876]
8. Thomassen E, Renshaw BR, Sims JE. (1999) Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine, 11 (6): 389-99. [PMID:10346978]
9. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X. (2003) SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol, 4 (9): 920-7. [PMID:12925853]
Immunoglobulin-like family of IL-1 receptors: single Ig and TIR domain containing. Last modified on 22/11/2017. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2969.
