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IL3RA (Interleukin-3 Receptor alpha)

Identity

Other namesCD123
HGNC (Hugo) IL3RA
LocusID (NCBI) 3563
Location Xp22.33
Location_base_pair Starts at 1455509 and ends at 1501582 bp from pter ( according to and)  [Mapping]

DNA/RNA

Description The gene encoding interleukin-3 receptor is located in the pseudoautosomal region (PAR) at the end of the short arm of the X and Y chromosomes. The IL-3R alpha chain gene contains twelve exons and eleven introns that span an area of approximately 40 Kb. It is positioned near (190 Kbp) to the gene encoding for GM-CSFR alpha chain. Both the IL-3R alpha and GM-CSFR alpha genes display a similar structural organization, suggesting a common evolutionary origin for both genes.

Protein

Description The IL-3R alpha gene encodes a type I transmembrane protein of 41.3 KDa. The IL-3R alpha precursor chain protein is composed by 378 amino acids. Cleavage of the 18 amino acid signal peptide yelds a mature polypeptide chain of 360 amino acids, containing a 288 amino acid extracellular domain involved in IL-3 binding, a 20 amino acid transmembrane domain and a short cytoplasmic tail of 52 amino acids. The extracellular domain is composed by two regions: a N-terminal region of about 100 amino acids, whose sequence exhibits a great similarity to equivalent regions of the GM-CSF and IL-5 receptor alpha-chains; a region, proximal to the transmembrane domain, that contains four conserved cysteine residues and a WSXWS motif, common to other members of this cytokine receptor family. The ligand binding domain consists of about 200 amino acid residue cytokine receptor motifs (CRMs) made up of two Ig-like folding domains. The IL-3R alpha chain is highly glycosylated: six potential N-glycosylation sites have been detected in the extracellular domain. Due to the high glycosylation, the natural IL-3R alpha protein exhibit a MW of about 70 KDa. N-glycosylation is necessary for both ligand binding and receptor signaling. The IL-3R alpha cytoplasmic tail contains a short proline motif, similar to box 1 of the IL-3R beta common chain.
Expression At the level of the hematopoietic system IL-3R alpha expression was described on bone marrow CD34+ cells (including primitive multipotential and committed progenitors), granulocytes, monocytes/macrophages, megakaryocytes and B-lymphocytes. Although the IL-3R alpha is expressed on the large majority of progenitor cells, it does not seem to be expressed on the stem cell fraction. The large majority of CD34+ cells possess IL-3R alpha, but its expression is lost during the initial steps of erythroid differentiation, while its expression is maintained up to terminal stages of granulo-monocytic differentiation. The IL-3R alpha is also a distinctive marker of the "lymphoid" dendritic cells present in peripheral blood. IL-3R alpha expression has also been described in several cell types outside the hemopoeitic system, including endothelial cells, fibroblasts and smooth muscle cells.
Localisation functional mature IL-3R alpha is located at the level of the plasma membrane where it forms a molecular complex with the IL-3R beta chain.
Function IL-3R alpha function can be defined by the activity of its ligand interleukin-3. IL-3 is a multipotent cytokine that promotes the development of hemopoietic progenitors into cells of the erythroid, myeloid and lymphoid lineages. In in vitro colony forming assays IL-3 supports the colony formation by virtually all types of hemopoeitic progenitors, including CFU-GEMM, CFU-GM, CFU-G, CFU-M, CFU-Mk, CFU-E and BFU-E.

Mutations

Note No mutations of the IL-3Ra gene have been reported in hematological and non hematological human malignancies. Elevated IL-3Ra expression has been reported in about 45% of patients with acute myeloid leukemia and in 40% of patients with acute B lymphoid leukemia. An high IL-3Ra expression has been reported also in hairy cell leukemia.

External links

Nomenclature
HGNC (Hugo)IL3RA   6012
Cards
AtlasIL3RAID40959chXp22Yp13
Entrez_Gene (NCBI)IL3RA  3563  interleukin 3 receptor, alpha (low affinity)
GeneCards (Weizmann)IL3RA
Ensembl hg19 (Hinxton)ENSG00000185291 [Gene_View]  chrX:1455509-1501582 [Contig_View]  IL3RA [Vega]
Ensembl hg38 (Hinxton)ENSG00000185291 [Gene_View]  chrX:1455509-1501582 [Contig_View]  IL3RA [Vega]
ICGC DataPortalENSG00000185291
cBioPortalIL3RA
AceView (NCBI)IL3RA
Genatlas (Paris)IL3RA
WikiGenes3563
SOURCE (Princeton)IL3RA
Genomic and cartography
GoldenPath hg19 (UCSC)IL3RA  -     chrX:1455509-1501582 +  Xp22.3   [Description]    (and)
GoldenPath hg38 (UCSC)IL3RA  -     Xp22.3   [Description]    (hg38-Dec_2013)
EnsemblIL3RA - Xp22.3 [CytoView hg19]  IL3RA - Xp22.3 [CytoView hg38]
Mapping of homologs : NCBIIL3RA [Mapview hg19]  IL3RA [Mapview hg38]
OMIM308385   430000   
Gene and transcription
Genbank (Entrez)AI765858 AK290568 AW452270 BC035407 EU176623
RefSeq transcript (Entrez)NM_001267713 NM_002183
RefSeq genomic (Entrez)NC_000023 NC_000024 NC_018934 NT_167201 NT_187358 NW_001841157 NW_004929437
Consensus coding sequences : CCDS (NCBI)IL3RA
Cluster EST : UnigeneHs.632790 [ NCBI ]
CGAP (NCI)Hs.632790
Alternative Splicing : Fast-db (Paris)GSHG0032975
Alternative Splicing GalleryENSG00000185291
Gene ExpressionIL3RA [ NCBI-GEO ]     IL3RA [ SEEK ]   IL3RA [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP26951 (Uniprot)
NextProtP26951  [Medical]
With graphics : InterProP26951
Splice isoforms : SwissVarP26951 (Swissvar)
Domaine pattern : Prosite (Expaxy)HEMATOPO_REC_S_F2 (PS01356)   
Domains : Interpro (EBI)Fibronectin_type3    Ig-like_fold    IL-6_rcpt_alpha-bd    Short_hematopoietin_rcpt_2_CS   
Related proteins : CluSTrP26951
Domain families : Pfam (Sanger)IL6Ra-bind (PF09240)   
Domain families : Pfam (NCBI)pfam09240   
DMDM Disease mutations3563
Blocks (Seattle)P26951
PDB (SRS)4JZJ   
PDB (PDBSum)4JZJ   
PDB (IMB)4JZJ   
PDB (RSDB)4JZJ   
Human Protein AtlasENSG00000185291
Peptide AtlasP26951
HPRD02392
IPIIPI00003058   IPI00553194   
Protein Interaction databases
DIP (DOE-UCLA)P26951
IntAct (EBI)P26951
FunCoupENSG00000185291
BioGRIDIL3RA
IntegromeDBIL3RA
STRING (EMBL)IL3RA
Ontologies - Pathways
QuickGOP26951
Ontology : AmiGOinterleukin-3 receptor activity  plasma membrane  integral component of membrane  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  
Ontology : EGO-EBIinterleukin-3 receptor activity  plasma membrane  integral component of membrane  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  
Pathways : BIOCARTARegulation of BAD phosphorylation [Genes]    IL 3 signaling pathway [Genes]   
Pathways : KEGGCytokine-cytokine receptor interaction    PI3K-Akt signaling pathway    Apoptosis    Jak-STAT signaling pathway    Hematopoietic cell lineage   
REACTOMEP26951 [protein]
REACTOME PathwaysREACT_6900 Immune System [pathway]
Protein Interaction DatabaseIL3RA
DoCM (Curated mutations)IL3RA
Wikipedia pathwaysIL3RA
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerIL3RA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)IL3RA
dbVarIL3RA
ClinVarIL3RA
1000_GenomesIL3RA 
Exome Variant ServerIL3RA
SNP (GeneSNP Utah)IL3RA
SNP : HGBaseIL3RA
Genetic variants : HAPMAPIL3RA
Genomic VariantsIL3RA  IL3RA [DGVbeta]
Mutations
ICGC Data PortalENSG00000185291 
Somatic Mutations in Cancer : COSMICIL3RA 
CONAN: Copy Number AnalysisIL3RA 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)X:1455509-1501582
Mutations and Diseases : HGMDIL3RA
OMIM308385    430000   
MedgenIL3RA
NextProtP26951 [Medical]
GENETestsIL3RA
Disease Genetic AssociationIL3RA
Huge Navigator IL3RA [HugePedia]  IL3RA [HugeCancerGEM]
snp3D : Map Gene to Disease3563
DGIdb (Drug Gene Interaction db)IL3RA
General knowledge
Homologs : HomoloGeneIL3RA
Homology/Alignments : Family Browser (UCSC)IL3RA
Phylogenetic Trees/Animal Genes : TreeFamIL3RA
Chemical/Protein Interactions : CTD3563
Chemical/Pharm GKB GenePA29831
Clinical trialIL3RA
Cancer Resource (Charite)ENSG00000185291
Other databases
Probes
Litterature
PubMed61 Pubmed reference(s) in Entrez
CoreMineIL3RA
GoPubMedIL3RA
iHOPIL3RA

Bibliography

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PMID 1833064
 
A cytokine receptor gene cluster in the X-Y pseudoautosomal region?
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PMID 8213838
 
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PMID 7887951
 
Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding.
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The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells.
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PMID 11021753
 
Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival.
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PMID 10949031
 
Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
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Cell. 2001 ; 104 (2) : 291-300.
PMID 11207369
 
Expression of interleukin 3 and granulocyte-macrophage colony-stimulating factor receptor common chain betac, betaIT in normal haematopoiesis: lineage specificity and proliferation-independent induction.
Militi S, Riccioni R, Parolini I, Sposi NM, Samoggia P, Pelosi E, Testa U, Peschle C
British journal of haematology. 2000 ; 111 (2) : 441-451.
PMID 11122083
 
Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies.
Muˆ±oz L, Nomdedˆ©u JF, Lˆ„pez O, Carnicer MJ, Bellido M, Aventˆ‚n A, Brunet S, Sierra J
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PMID 11726317
 
Identification of primary structural features that define the differential actions of IL-3 and GM-CSF receptors.
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PMID 12384414
 
Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis.
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PMID 12351411
 
Analysis of the 5' promoters for human IL-3 and GM-CSF receptor alpha genes.
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Biochemical and biophysical research communications. 2003 ; 300 (2) : 600-608.
PMID 12504125
 
IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease.
Wong S, McLaughlin J, Cheng D, Shannon K, Robb L, Witte ON
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (20) : 11630-11635.
PMID 14500898
 
Regulation of myeloid development and function by colony stimulating factors.
Barreda DR, Hanington PC, Belosevic M
Developmental and comparative immunology. 2004 ; 28 (5) : 509-554.
PMID 15062647
 
Immunophenotypic features of acute myeloid leukemias overexpressing the interleukin 3 receptor alpha chain.
Riccioni R, Rossini A, Calabrˆ¾ L, Diverio D, Pasquini L, Lococo F, Peschle C, Testa U
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PMID 15370201
 
Interleukin-3 receptor in acute leukemia.
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PMID 14671644
 
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Contributor(s)

Written05-2005Ugo Testa
Department of Hematology and Oncology, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy

Citation

This paper should be referenced as such :
Testa, U
IL3RA (interleukin-3 receptor alpha)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):227-228.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/IL3RAID40959chXp22Yp13.html

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