IL22RA1 (interleukin 22 receptor, alpha 1)
2010-02-01 Pascal Gelebart , Raymond Lai AffiliationDepartment of Laboratory Medicine, Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
Identity
HGNC
LOCATION
1p36.11
LOCUSID
ALIAS
CRF2-9,IL22R,IL22R1
FUSION GENES
DNA/RNA
Representation of the IL22RA1 gene organization. IL22RA1 gene and RNA.
Description
The gene spans a region of 23.3 kb including seven exons.
Transcription
One only transcript form containing 7 exons has been described. The last exon is partially untranslated. The transcript length is 1725 nucleotides, encoding a protein of 594 amino acid residues.
Pseudogene
None.
Proteins
IL22RA1 protein organization and localization. IL22RA1 protein domains.
Description
IL22RA1 is composed of 574 amino acid residues, and the predicted molecular weight of the immature protein is 63 kDa. IL22RA1 protein is composed of six putative domains, including the signal peptide (residue 1 to 15), the extracellular domain (residue 16 to 228), the transmembrane domain (residue 229 to 249), the cytoplasmic domain (residue 250 to 574), and two fibronectin type-III domains (residue 18-115 and 141-221).
Crystal structure of IL22RA1 with IL22 at 1.9 A resolution. Adapted from PDB (access number: 3DLQ).
Expression
IL22RA1 expression is relatively restricted, being found at the highest level in the pancreas, small intestine, colon, kidney, and liver. Importantly, IL22RA1 is not detectable in normal immune cells, including monocytes, B-cells, T-cells, natural killer cells, macrophages and dendritic cells, cell types that are normally found in the bone marrow, peripheral blood, thymus and spleen.
FACS analysis of IL22RA1 expression in peripheral mononuclear cells from healthy donor.
Localisation
IL22RA1 is localized at the plasma membrane.
Localization of IL22RA1 by immunufluorescence confocal microscopy in ALK+ALCL cells.
Function
IL22RA1 is one of the subunits of the IL20, IL22 and IL24 receptor complex. Cytokine binding to IL22RA1 results in its aggregation, which activates the associated JAK via its autophosphorylation. This in turn leads to the phosphorylation and activation of STAT proteins. Subsequently, phosphorylated STAT proteins dimerize and translocate to the nucleus to modulate the transcription of various target genes.
IL22RA1 signaling.
Mutations
Note
Site-directed mutagenesis experiments have revealed critical amino acid residues involved in its binding to IL22. Specifically, mutation of residue 58 from K to A reduces the binding of IL22. Mutation of the residue 60 from Y to A or R results in a complete loss of response to IL22.
Natural IL22RA1 variants have been reported, including those carrying mutations at the residue 130 (S to P), 205 (V to I), 209 (A to S), 222 (L to P), 407 (M to V) and 518 (R to G).
Natural IL22RA1 variants have been reported, including those carrying mutations at the residue 130 (S to P), 205 (V to I), 209 (A to S), 222 (L to P), 407 (M to V) and 518 (R to G).
Implicated in
Entity name
ALK-positive anaplastic large cell lymphoma (ALK+ALCL)
Disease
Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), or ALK+ALCL, is a specific type of non-Hodgkin lymphoma characterized by the T/null-cell immunophenotype, consistent expression of CD30 and reciprocal chromosomal translocations involving the ALK gene. In most cases, the chromosomal translocation is that of the t(2;5)(p23;q35), which leads to the juxtaposition of the nucleophosmin (NPM) gene at 5q35 with the ALK gene at 2p23. Mounting evidence suggests that the resulted oncogenic fusion protein, NPM-ALK, plays crucial roles in the pathogenesis of these tumors.
Prognosis
Patients with ALK+ALCL are typically treated with combination chemotherapy containing doxorubicin. ALK+ALCL represents one of the most common pediatric lymphoid malignancies. The prognosis of pediatric ALK+ALCL patients is significant better than that of adult patients.
Cytogenetics
t(2;5)(p23;q35) in most ALK+ALCL patients; other translocation variants have been described.
Hybrid gene
NPM-ALK
Representation of the NPM-ALK oncoprotein organization and sequence.
Fusion protein
NPM-ALK
Structure of the oncogenic fusion protein NPM-ALK.
Oncogenesis
Aberrant expression of IL22RA1 in ALK+ALCL lymphoma cells allows these cells to be responsive to IL-22 stimulation, which further stimulate STAT3 signaling and the growth of these cells. Blocking the IL-22 signaling pathway using a neutralizing antibody has been shown to significantly decrease the growth of ALK+ALCL cells in-vitro. The aberrant expression of IL22RA1 in ALK+ALCL is dependent on the expression of NPM-ALK, since siRNA to downregulate NPM-ALK dramatically shut down IL22RA1 expression.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17519389 | 2007 | Pathobiology of ALK+ anaplastic large-cell lymphoma. | Amin HM et al |
| 18509351 | 2008 | Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma. | Bard JD et al |
| 18675809 | 2008 | Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism. | Bleicher L et al |
| 19632985 | 2009 | New activation modus of STAT3: a tyrosine-less region of the interleukin-22 receptor recruits STAT3 by interacting with its coiled-coil domain. | Dumoutier L et al |
| 19393422 | 2009 | Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis. | Endam LM et al |
| 11035029 | 2001 | Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. | Kotenko SV et al |
| 12407026 | 2002 | IL-22, in contrast to IL-10, does not induce Ig production, due to absence of a functional IL-22 receptor on activated human B cells. | Lécart S et al |
| 11706020 | 2002 | Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. | Wang M et al |
| 18024507 | 2008 | Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains. | de Oliveira Neto M et al |
Other Information
Locus ID:
NCBI: 58985
MIM: 605457
HGNC: 13700
Ensembl: ENSG00000142677
Variants:
dbSNP: 58985
ClinVar: 58985
TCGA: ENSG00000142677
COSMIC: IL22RA1
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000142677 | ENST00000270800 | Q8N6P7 |
Expression (GTEx)
Pathways
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38811550 | 2024 | Pancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis. | 1 |
| 38811550 | 2024 | Pancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis. | 1 |
| 37511050 | 2023 | Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE. | 0 |
| 37511050 | 2023 | Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE. | 0 |
| 34920229 | 2022 | Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages. | 1 |
| 35422799 | 2022 | Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection. | 8 |
| 35838587 | 2022 | Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C. | 0 |
| 35970323 | 2022 | Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis. | 6 |
| 34920229 | 2022 | Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages. | 1 |
| 35422799 | 2022 | Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection. | 8 |
| 35838587 | 2022 | Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C. | 0 |
| 35970323 | 2022 | Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis. | 6 |
| 31879195 | 2021 | Association of interleukin 22 receptor subunit alpha 1 gene polymorphisms with chronic rhinosinusitis. | 3 |
| 32636527 | 2021 | Targeting IL-22 and IL-22R protects against experimental osteoarthritis. | 5 |
| 34134925 | 2021 | High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer. | 1 |
Citation
Pascal Gelebart ; Raymond Lai
IL22RA1 (interleukin 22 receptor, alpha 1)
Atlas Genet Cytogenet Oncol Haematol. 2010-02-01
Online version: http://atlasgeneticsoncology.org/gene/44568/il22ra1
