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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
Entrez_Gene (NCBI)IL3RA  3563  interleukin 3 receptor, alpha (low affinity)
Cards
AtlasIL3RAID40959chXp22Yp13
GeneCards (Weizmann)IL3RA
Ensembl (Hinxton)ENSG00000185291 [Gene_View]  chrX:1455509-1501582 [Contig_View]  IL3RA [Vega]
AceView (NCBI)IL3RA
Genatlas (Paris)IL3RA
SOURCE (Stanford)NM_001267713 NM_002183
Genomic and cartography
GoldenPath (UCSC)IL3RA  -  Xp22.33   chrX:1455509-1501582 +  Xp22.3   [Description]    (and)
EnsemblIL3RA - Xp22.3 [CytoView]
Mapping of homologs : NCBIIL3RA [Mapview]
OMIM308385   430000   
Gene and transcription
Genbank (Entrez)AI765858 AK290568 AW452270 BC035407 EU176623
RefSeq transcript (SRS)NM_001267713 NM_002183
RefSeq transcript (Entrez)NM_001267713 NM_002183
RefSeq genomic (SRS)NC_000023 NC_000024 NC_018934 NT_167196 NT_167204 NW_001841157 NW_004078117
RefSeq genomic (Entrez)NC_000023 NC_000024 NC_018934 NT_167196 NT_167204 NW_001841157 NW_004078117
Consensus coding sequences : CCDS (NCBI)IL3RA
Cluster EST : UnigeneHs.632790 [ SRS ] Hs.632790 [ NCBI ]
CGAP (NCI)Hs.632790
Alternative Splicing : Fast-db (Paris)GSHG0032975
Alternative Splicing GalleryENSG00000185291
Gene ExpressionIL3RA [ NCBI-GEO ]   IL3RA [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP26951 (SRS) P26951 (Uniprot)
NextProtP26951
With graphics : InterProP26951
Splice isoforms : SwissVarP26951(Swissvar)
Domaine pattern : Prosite (SRS)HEMATOPO_REC_S_F2 (PS01356)   
Domaine pattern : Prosite (Expaxy)HEMATOPO_REC_S_F2 (PS01356)   
Domains : Interpro (SRS)Fibronectin_type3    Ig-like_fold    IL6_recept-bd    Short_hematopoietin_rcpt_2_CS   
Domains : Interpro (EBI)Fibronectin_type3    Ig-like_fold    IL6_recept-bd    Short_hematopoietin_rcpt_2_CS   
Related proteins : CluSTrP26951
Domain families : Pfam (SRS)IL6Ra-bind (PF09240)   
Domain families : Pfam (Sanger)IL6Ra-bind (PF09240)   
Domain families : Pfam (NCBI)pfam09240   
DMDM3563
Blocks (Seattle)P26951
Human Protein AtlasENSG00000185291
HPRD02392
IPIIPI00003058   IPI00553194   
Protein Interaction databases
DIP (DOE-UCLA)P26951
IntAct (EBI)P26951
FunCoupENSG00000185291
REACTOMEIL3RA
Protein Interaction Database3563
BioGRIDIL3RA
InParanoidP26951
Interologous Interaction database P26951
IntegromeDBIL3RA
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)IL3RA
SNP (GeneSNP Utah)IL3RA
SNP : HGBaseIL3RA
Genetic variants : HAPMAPIL3RA
Somatic Mutations in Cancer : COSMICIL3RA 
CONAN: Copy Number AnalysisIL3RA 
Mutations and Diseases : HGMDIL3RA
OMIM308385    430000   
GENETests308385    430000   
Disease Genetic AssociationIL3RA
Huge Navigator IL3RA [HugePedia]  IL3RA [HugeCancerGEM]
Genomic VariantsIL3RA  IL3RA [DGVbeta]
snp3D : Map Gene to Disease3563
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
Ontology : AmiGOinterleukin-3 receptor activity  plasma membrane  integral to membrane  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  
Ontology : EGO-EBIinterleukin-3 receptor activity  plasma membrane  integral to membrane  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  
Pathways : BIOCARTARegulation of BAD phosphorylation [Genes]    IL 3 signaling pathway [Genes]   
Pathways : KEGGHematopoietic cell lineageCytokine-cytokine receptor interactionJak-STAT signaling pathwayApoptosis
Other databases
Probes
Litterature
PubMed54 Pubmed reference(s) in Entrez
PubGeneIL3RA
iHOPIL3RA

Bibliography

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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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Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival.
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Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies.
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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 14500898
 
Regulation of myeloid development and function by colony stimulating factors.
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PMID 15062647
 
Immunophenotypic features of acute myeloid leukemias overexpressing the interleukin 3 receptor alpha chain.
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Interleukin-3 receptor in acute leukemia.
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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. May 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/IL3RAID40959chXp22Yp13.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38211/1/05-2005-IL3RAID40959chXp22Yp13.pdf   [ Bibliographic record ]

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indexed on : Wed May 1 12:54:24 CEST 2013
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