Organization of the human interleukin-1 receptor antagonist gene IL1HY1

Abstract

The interleukin (IL)-1 family of proteins plays an important role in inflammatory and defense mechanisms. The recently characterized IL1HY1 cDNA encodes a new member of the IL-1 receptor antagonist family (IL-1ra). In this report, we describe the complete nucleotide sequence of the human IL1HY1 gene. We sequenced approximately 7,600 nucleotides and found four coding exons ranging in size from 55 to 2,288 nucleotides. The 5' untranslated region is formed by one of two alternatively used exons and one invariably present exon which also contains the region encoding the first nine amino acids of the protein. IL1HY1 and IL-1ra intron positions are well conserved within the protein-coding region, providing evidence that these genes arose from a duplication of a primordial IL-1 receptor antagonist gene.

The chicken IL-1 family: evolution in the context of the studied vertebrate lineage

“…Since this subject was last reviewed almost a decade ago (Huising et al 2004), our work in the chicken has identified two IL-1 receptor antagonist genes for the first time in a non-mammalian species (Gibson et al 2012a; Gibson et al 2012b). The fact that they reside at an alternative locus to IL-1β yet retain structural and functional similarities with their mammalian orthologues suggests that the previous conjecture on the evolution of these two receptor antagonists is likely to be incorrect (Mulero et al 2000). An IL-1β antagonist in rainbow trout (Wang et al 2009) and three IL-1 genes in lizards that group with the chicken, human and mouse receptor antagonists (Gibson et al 2012a) have also been identified.…”

“…IL-36RN also interacts with the orphan receptor SIGIRR to downregulate inflammation through an as yet unelucidated mechanism (Costelloe et al 2008). The gene for IL-36RN is present in the genome sequence of over 30 mammalian species and was previously proposed to have arisen following gene duplication from IL-1RN in the ancestral species of the mammalian lineage (Mulero et al 2000). The chicken is the only non-mammalian species in which it has been identified to date (Gibson et al 2012b).…”

Innate Immunity Mediated by the Cytokine IL-1 Homologue 4 (IL-1H4/IL-1F7) Induces IL-12-Dependent Adaptive and Profound Antitumor Immunity

“…The proposed nomenclature for the IL-1 family are IL-1F1 (IL-1␣), IL-1F2 (IL-1␤), IL-1F3 (IL-1Ra), IL-1F4 (IL-18), IL-1F5 (IL-1H3, IL-1Hy1, FIL1␦, IL-1RP3, IL-1L1, and IL-1␦), IL-1F6 (FIL1⑀), IL-1F7 (human IL-1 homologue (IL-1H4), FIL1, IL-1RP1, and IL-1H), IL-1F8 (IL-1H2 and FIL), IL-1F9 (IL-1H1, IL-1RP2, and IL-1⑀), and IL-1F10 (IL-1Hy2 and FKSG75) (17)(18)(19)(20)(21)(22)(23)(24). Preliminary studies showed that these novel members also do not contain a hydrophobic leader sequence.…”

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity

“…The new members of the IL-1 family are derived from a common ancestor, as are IL-1 and IL-18 (11,12). Except for IL-18, each maps to the same region on human chromosome 2 (4,(11)(12)(13). On the basis of their structure these IL-1 family members potentially can act as agonistic or antagonistic ligands for members of the IL-1 receptor family; however, their biological function is presently unknown.…”