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IL22RA1 (interleukin 22 receptor, alpha 1)

Written2010-02Pascal Gelebart, Raymond Lai
Department of Laboratory Medicine, Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada

(Note : for Links provided by Atlas : click)

Identity

Alias_namesIL22R
interleukin 22 receptor
interleukin 22 receptor, alpha 1
Alias_symbol (synonym)CRF2-9
Other aliasIL22R1
HGNC (Hugo) IL22RA1
LocusID (NCBI) 58985
Atlas_Id 44568
Location 1p36.11  [Link to chromosome band 1p36]
Location_base_pair Starts at 24446261 and ends at 24469775 bp from pter ( according to hg19-Feb_2009)  [Mapping IL22RA1.png]
Fusion genes
(updated 2016)
IL22RA1 (1p36.11) / MESDC2 (15q25.1)RNF213 (17q25.3) / IL22RA1 (1p36.11)

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.

Protein

 
  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).

Implicated in

Note
  
Entity 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/Mutated Gene NPM-ALK
 
Representation of the NPM-ALK oncoprotein organization and sequence.
Abnormal 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.
  

Bibliography

Pathobiology of ALK+ anaplastic large-cell lymphoma.
Amin HM, Lai R.
Blood. 2007 Oct 1;110(7):2259-67. Epub 2007 May 22.
PMID 17519389
 
Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma.
Bard JD, Gelebart P, Anand M, Amin HM, Lai R.
Leukemia. 2008 Aug;22(8):1595-603. Epub 2008 May 29.
PMID 18509351
 
Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism.
Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L, Renauld JC, Polikarpov I.
FEBS Lett. 2008 Sep 3;582(20):2985-92. Epub 2008 Aug 7.
PMID 18675809
 
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, de Meester C, Tavernier J, Renauld JC.
J Biol Chem. 2009 Sep 25;284(39):26377-84. Epub 2009 Jul 24.
PMID 19632985
 
Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis.
Endam LM, Bosse Y, Filali-Mouhim A, Cormier C, Boisvert P, Boulet LP, Hudson TJ, Desrosiers M.
Otolaryngol Head Neck Surg. 2009 May;140(5):741-7. Epub 2009 Feb 28.
PMID 19393422
 
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, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H, Donnelly RP, Pestka S.
J Biol Chem. 2001 Jan 26;276(4):2725-32. Epub 2000 Oct 16.
PMID 11035029
 
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.
Lecart S, Morel F, Noraz N, Pene J, Garcia M, Boniface K, Lecron JC, Yssel H.
Int Immunol. 2002 Nov;14(11):1351-6.
PMID 12407026
 
Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2.
Wang M, Tan Z, Zhang R, Kotenko SV, Liang P.
J Biol Chem. 2002 Mar 1;277(9):7341-7. Epub 2001 Nov 12.
PMID 11706020
 
Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains.
de Oliveira Neto M, Ferreira JR Jr, Colau D, Fischer H, Nascimento AS, Craievich AF, Dumoutier L, Renauld JC, Polikarpov I.
Biophys J. 2008 Mar 1;94(5):1754-65. Epub 2007 Nov 16.
PMID 18024507
 

Citation

This paper should be referenced as such :
Gelebart, P ; Lai, R
IL22RA1 (interleukin 22 receptor, alpha 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1106-1110.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/IL22RA1ID44568ch1p36.html


External links

Nomenclature
HGNC (Hugo)IL22RA1   13700
Cards
AtlasIL22RA1ID44568ch1p36
Entrez_Gene (NCBI)IL22RA1  58985  interleukin 22 receptor subunit alpha 1
AliasesCRF2-9; IL22R; IL22R1
GeneCards (Weizmann)IL22RA1
Ensembl hg19 (Hinxton)ENSG00000142677 [Gene_View]  chr1:24446261-24469775 [Contig_View]  IL22RA1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000142677 [Gene_View]  chr1:24446261-24469775 [Contig_View]  IL22RA1 [Vega]
ICGC DataPortalENSG00000142677
TCGA cBioPortalIL22RA1
AceView (NCBI)IL22RA1
Genatlas (Paris)IL22RA1
WikiGenes58985
SOURCE (Princeton)IL22RA1
Genetics Home Reference (NIH)IL22RA1
Genomic and cartography
GoldenPath hg19 (UCSC)IL22RA1  -     chr1:24446261-24469775 -  1p36.11   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)IL22RA1  -     1p36.11   [Description]    (hg38-Dec_2013)
EnsemblIL22RA1 - 1p36.11 [CytoView hg19]  IL22RA1 - 1p36.11 [CytoView hg38]
Mapping of homologs : NCBIIL22RA1 [Mapview hg19]  IL22RA1 [Mapview hg38]
OMIM605457   
Gene and transcription
Genbank (Entrez)AF286095 AK226001 AK292204 AK304454 AK308522
RefSeq transcript (Entrez)NM_021258
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_032977 NW_004929289
Consensus coding sequences : CCDS (NCBI)IL22RA1
Cluster EST : UnigeneHs.110915 [ NCBI ]
CGAP (NCI)Hs.110915
Alternative Splicing GalleryENSG00000142677
Gene ExpressionIL22RA1 [ NCBI-GEO ]   IL22RA1 [ EBI - ARRAY_EXPRESS ]   IL22RA1 [ SEEK ]   IL22RA1 [ MEM ]
Gene Expression Viewer (FireBrowse)IL22RA1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)58985
GTEX Portal (Tissue expression)IL22RA1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N6P7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8N6P7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8N6P7
Splice isoforms : SwissVarQ8N6P7
PhosPhoSitePlusQ8N6P7
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)   
Domains : Interpro (EBI)FN3_dom    Ig-like_fold    Interferon/interleukin_rcp_dom   
Domain families : Pfam (Sanger)Interfer-bind (PF09294)    Tissue_fac (PF01108)   
Domain families : Pfam (NCBI)pfam09294    pfam01108   
Conserved Domain (NCBI)IL22RA1
DMDM Disease mutations58985
Blocks (Seattle)IL22RA1
PDB (SRS)3DGC    3DLQ   
PDB (PDBSum)3DGC    3DLQ   
PDB (IMB)3DGC    3DLQ   
PDB (RSDB)3DGC    3DLQ   
Structural Biology KnowledgeBase3DGC    3DLQ   
SCOP (Structural Classification of Proteins)3DGC    3DLQ   
CATH (Classification of proteins structures)3DGC    3DLQ   
SuperfamilyQ8N6P7
Human Protein AtlasENSG00000142677
Peptide AtlasQ8N6P7
HPRD16108
IPIIPI00297430   
Protein Interaction databases
DIP (DOE-UCLA)Q8N6P7
IntAct (EBI)Q8N6P7
FunCoupENSG00000142677
BioGRIDIL22RA1
STRING (EMBL)IL22RA1
ZODIACIL22RA1
Ontologies - Pathways
QuickGOQ8N6P7
Ontology : AmiGOinterferon receptor activity  protein binding  plasma membrane  plasma membrane  biological_process  integral component of membrane  cytokine-mediated signaling pathway  interleukin-20 binding  defense response to Gram-negative bacterium  
Ontology : EGO-EBIinterferon receptor activity  protein binding  plasma membrane  plasma membrane  biological_process  integral component of membrane  cytokine-mediated signaling pathway  interleukin-20 binding  defense response to Gram-negative bacterium  
Pathways : KEGGCytokine-cytokine receptor interaction    Jak-STAT signaling pathway   
REACTOMEQ8N6P7 [protein]
REACTOME Pathways8854691 [pathway]   
NDEx NetworkIL22RA1
Atlas of Cancer Signalling NetworkIL22RA1
Wikipedia pathwaysIL22RA1
Orthology - Evolution
OrthoDB58985
GeneTree (enSembl)ENSG00000142677
Phylogenetic Trees/Animal Genes : TreeFamIL22RA1
HOVERGENQ8N6P7
HOGENOMQ8N6P7
Homologs : HomoloGeneIL22RA1
Homology/Alignments : Family Browser (UCSC)IL22RA1
Gene fusions - Rearrangements
Fusion : MitelmanRNF213/IL22RA1 [17q25.3/1p36.11]  [t(1;17)(p36;q25)]  
Fusion: TCGARNF213 17q25.3 IL22RA1 1p36.11 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerIL22RA1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)IL22RA1
dbVarIL22RA1
ClinVarIL22RA1
1000_GenomesIL22RA1 
Exome Variant ServerIL22RA1
ExAC (Exome Aggregation Consortium)IL22RA1 (select the gene name)
Genetic variants : HAPMAP58985
Genomic Variants (DGV)IL22RA1 [DGVbeta]
DECIPHER (Syndromes)1:24446261-24469775  ENSG00000142677
CONAN: Copy Number AnalysisIL22RA1 
Mutations
ICGC Data PortalIL22RA1 
TCGA Data PortalIL22RA1 
Broad Tumor PortalIL22RA1
OASIS PortalIL22RA1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICIL22RA1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDIL22RA1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch IL22RA1
DgiDB (Drug Gene Interaction Database)IL22RA1
DoCM (Curated mutations)IL22RA1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)IL22RA1 (select a term)
intoGenIL22RA1
NCG5 (London)IL22RA1
Cancer3DIL22RA1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605457   
Orphanet
MedgenIL22RA1
Genetic Testing Registry IL22RA1
NextProtQ8N6P7 [Medical]
TSGene58985
GENETestsIL22RA1
Huge Navigator IL22RA1 [HugePedia]
snp3D : Map Gene to Disease58985
BioCentury BCIQIL22RA1
ClinGenIL22RA1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD58985
Chemical/Pharm GKB GenePA29823
Clinical trialIL22RA1
Miscellaneous
canSAR (ICR)IL22RA1 (select the gene name)
Probes
Litterature
PubMed31 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineIL22RA1
EVEXIL22RA1
GoPubMedIL22RA1
iHOPIL22RA1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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