Interleukin 1 receptor antagonist

Interleukin 1 receptor antagonist
Rendering of 1ILR
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ILR, 1ILT, 1IRA, 1IRP, 1ITN, 2IRT
Identifiers
Symbols	IL1RN ; DIRA; ICIL-1RA; IL-1RN; IL-1ra; IL-1ra3; IL1F3; IL1RA; IRAP; MVCD4
External IDs	OMIM: 147679 MGI: 96547 HomoloGene: 11163 GeneCards: IL1RN Gene
Gene ontology Molecular function • cytokine activity • interleukin-1 receptor binding • interleukin-1, Type I receptor binding • interleukin-1, Type II receptor binding • interleukin-1 receptor antagonist activity • interleukin-1 Type I receptor antagonist activity • interleukin-1 Type II receptor antagonist activity Cellular component • extracellular space • intracellular • cytoplasm • plasma membrane • extracellular exosome Biological process • fever generation • negative regulation of cytokine-mediated signaling pathway • inflammatory response to antigenic stimulus • chronic inflammatory response to antigenic stimulus • lipid metabolic process • acute-phase response • immune response • female pregnancy • memory • negative regulation of glutamate secretion • response to activity • sensory perception of pain • carboxylic acid metabolic process • insulin secretion • negative regulation of cell migration • response to lipopolysaccharide • negative regulation of heterotypic cell-cell adhesion • response to drug • response to starvation • negative regulation of apoptotic process • positive regulation of JUN kinase activity • negative regulation of membrane potential • response to glucocorticoid • response to interleukin-1 • response to interleukin-4 • cellular response to norepinephrine stimulus • negative regulation of interleukin-1-mediated signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3557	16181
Ensembl	ENSG00000136689	ENSMUSG00000026981
UniProt	P18510	P25085
RefSeq (mRNA)	NM_000577	NM_001039701
RefSeq (protein)	NP_000568	NP_001034790
Location (UCSC)	Chr 2: 113.11 – 113.13 Mb	Chr 2: 24.34 – 24.35 Mb
PubMed search	[1]	[2]

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.

IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1 receptor (IL-1R). IL-1R is the same receptor that binds interleukin 1 (IL-1). Hence IL-1RA prevents IL-1 from sending a signal to that cell.

Function

IL-1RA is a member of the interleukin 1 cytokine family. IL1Ra is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1β. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

Clinical significance

A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer.

Mutations in the IL1RN gene results in a rare disease called deficiency of the interleukin-1–receptor antagonist (DIRA). Variants of the IL1RN gene is also associated with risk of schizophrenia. Elevated levels of IL1RN has been found in serum of schizophrenia patients.

An interleukin 1 receptor antagonist is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra, which is a human recombinant form of IL-1RA. In terms of protein similarities, IL-1β is more closely related to IL-1RA than it is to IL- 1α. The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA.

Use in horses

Interleukin 1 receptor antagonist is used in horses for the treatment of equine lameness secondary to joint injury.

External links

• Interleukin 1 Receptor Antagonist Protein at the US National Library of Medicine Medical Subject Headings (MeSH)