Interleukin-1 propeptide (IPR003502)

Short name: IL-1_propep

Overlapping homologous superfamilies


Domain relationships



Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis [PMID: 2969618]. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors [PMID: 8702856]. The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location [PMID: 1833184]. The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B [PMID: 2602367] have been solved, showing them to share the same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors [PMID: 1738162]. The beta-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain [PMID: 1826022]. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors [PMID: 1826022]. A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta [PMID: 1339315].

The N-terminal of Interleukin-1 is approximately 115 amino acids long, it forms a propeptide that is cleaved off to release the active interleukin-1. This signature is for the propeptide.

GO terms

Biological Process

GO:0006955 immune response
GO:0006954 inflammatory response

Molecular Function

GO:0005149 interleukin-1 receptor binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.