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single Ig and TIR domain containing

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2969

Nomenclature: single Ig and TIR domain containing

Systematic Nomenclature: IL-1R8

Family: Immunoglobulin-like family of IL-1 receptors

Gene and Protein Information Click here for help
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 Click here for help
single immunoglobulin and toll-interleukin 1 receptor (TIR) domain | single immunoglobulin domain IL1R1 related | TIR8
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

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Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
IL-37 {Sp: Human} Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist - - 6
Description: Interaction determined using fluorescence lifetime imaging–Förster resonance energy transfer (FLIM-FRET) and proximity ligation assay (PLA) studies in LPS-stimulated human PBMCs.
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].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
References:  4
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
Comment:  Expression determined by flow cytometry in human PBMCs.
References:  6
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Physiological Consequences of Altering Gene Expression Click here for help
Sigirr deficient mice display a hyperinflammatory phenotype in several disease models.
Species:  Mouse
References:  1-3
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].


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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]

How to cite this page

Immunoglobulin-like family of IL-1 receptors: single Ig and TIR domain containing. Last modified on 22/11/2017. Accessed on 20/05/2024. IUPHAR/BPS Guide to PHARMACOLOGY,