Download Gene Section IL22RA1 (interleukin 22 receptor, alpha 1)

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
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IL22RA1 (interleukin 22 receptor, alpha 1)
Pascal Gelebart, Raymond Lai
Department of Laboratory Medicine and Pathology, Cross Cancer Institute, University of Alberta,
Edmonton, Alberta, Canada (PG, RL)
Published in Atlas Database: February 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/IL22RA1ID44568ch1p36.html
DOI: 10.4267/2042/44908
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
nucleotides, encoding a protein of 594 amino acid
residues.
Other names: CRF2-9, IL22R, IL22R1
HGNC (Hugo): IL22RA1
Location: 1p36.11
Pseudogene
None.
Protein
DNA/RNA
Description
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 141221).
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
Representation of the IL22RA1 gene organization. IL22RA1 gene and RNA.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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IL22RA1 (interleukin 22 receptor, alpha 1)
Gelebart P, Lai R
IL22RA1 protein organization and localization. IL22RA1 protein domains.
Localization of IL22RA1 by immunufluorescence confocal microscopy in ALK+ALCL cells.
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.
Localisation
IL22RA1 is localized at the plasma membrane.
Crystal structure of IL22RA1 with IL22 at 1.9 A resolution.
Adapted from PDB (access number: 3DLQ).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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IL22RA1 (interleukin 22 receptor, alpha 1)
Gelebart P, Lai R
FACS analysis of IL22RA1 expression in peripheral mononuclear cells from healthy donor.
IL22RA1 signaling.
and translocate to the nucleus to modulate the
transcription of various target genes.
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
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Mutations
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
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IL22RA1 (interleukin 22 receptor, alpha 1)
Gelebart P, Lai R
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).
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/Mutated gene
NPM-ALK
Implicated in
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,
Representation of the NPM-ALK oncoprotein organization and sequence.
Abnormal protein
NPM-ALK
References
Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E,
Dickensheets H, Donnelly RP, Pestka S. 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. J Biol Chem. 2001 Jan 26;276(4):2725-32
Structure of the oncogenic fusion protein NPM-ALK.
Lécart S, Morel F, Noraz N, Pène J, Garcia M, Boniface K,
Lecron JC, Yssel H. 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. Int Immunol. 2002 Nov;14(11):1351-6
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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Wang M, Tan Z, Zhang R, Kotenko SV, Liang P. Interleukin 24
(MDA-7/MOB-5) signals through two heterodimeric receptors,
IL-22R1/IL-20R2 and IL-20R1/IL-20R2. J Biol Chem. 2002 Mar
1;277(9):7341-7
Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC.
Cloning of a new type II cytokine receptor activating signal
transducer and activator of transcription (STAT)1, STAT2 and
STAT3. Biochem J. 2003 Mar 1;370(Pt 2):391-6
Amin HM, Lai R. Pathobiology of ALK+ anaplastic large-cell
lymphoma. Blood. 2007 Oct 1;110(7):2259-67
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IL22RA1 (interleukin 22 receptor, alpha 1)
Gelebart P, Lai R
Bard JD, Gelebart P, Anand M, Amin HM, Lai R. Aberrant
expression of IL-22 receptor 1 and autocrine IL-22 stimulation
contribute to tumorigenicity in ALK+ anaplastic large cell
lymphoma. Leukemia. 2008 Aug;22(8):1595-603
interleukin-22 receptor recruits STAT3 by interacting with its
coiled-coil domain. J Biol Chem. 2009 Sep 25;284(39):2637784
Endam LM, Bossé Y, Filali-Mouhim A, Cormier C, Boisvert P,
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interleukin-22 receptor alpha-1 gene are associated with
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2009 May;140(5):741-7
Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L,
Renauld JC, Polikarpov I. Crystal structure of the IL-22/IL22R1 complex and its implications for the IL-22 signaling
mechanism. FEBS Lett. 2008 Sep 3;582(20):2985-92
de Oliveira Neto M, Ferreira JR Jr, Colau D, Fischer H,
Nascimento AS, Craievich AF, Dumoutier L, Renauld JC,
Polikarpov I. Interleukin-22 forms dimers that are recognized
by two interleukin-22R1 receptor chains. Biophys J. 2008 Mar
1;94(5):1754-65
This article should be referenced as such:
Gelebart P, Lai R. IL22RA1 (interleukin 22 receptor, alpha 1).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12):11061110.
Dumoutier L, de Meester C, Tavernier J, Renauld JC. New
activation modus of STAT3: a tyrosine-less region of the
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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