single Ig and TIR domain containing

Target id: 2969

Nomenclature: single Ig and TIR domain containing

Systematic Nomenclature: IL-1R8

Family: Immunoglobulin-like family of IL-1 receptors

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     single Ig and TIR domain containing has curated GtoImmuPdb data

Gene and Protein Information
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
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
IL-37 {Sp: Human} Hs Agonist - - 6
[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].
Immuno Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment: 
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 ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  acute-phase response (GO:0006953) ISS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  negative regulation of cytokine-mediated signaling pathway (GO:0001960) ISS
negative regulation of chemokine biosynthetic process (GO:0045079) ISS
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  negative regulation of chemokine biosynthetic process (GO:0045079) ISS
References: 
Physiological Consequences of Altering Gene Expression
Sigirr deficient mice display a hyperinflammatory phenotype in several disease models.
Species:  Mouse
Tissue: 
Technique: 
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].

References

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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. U.S.A.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. Nature551 (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. Cytokine11 (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 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2969.