Written | 2005-05 | Ugo Testa |
Department of Hematology, Oncology, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy |
Identity |
Alias (NCBI) | CD123 |
HGNC (Hugo) | IL3RA |
HGNC Alias symb | CD123 |
HGNC Previous name | "interleukin 3 receptor, alpha (low affinity)" |
LocusID (NCBI) | 3563 |
Atlas_Id | 40959 |
Location | Xp22.33 [Link to chromosome band Xp22] |
Location_base_pair | Starts at 1336785 and ends at 1382689 bp from pter ( according to and) [Mapping IL3RA.png] |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
CSF2RA (Xp22.33) / IL3RA (Xp22.33) |
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. |
Bibliography |
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Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. |
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Immunophenotypic features of acute myeloid leukemias overexpressing the interleukin 3 receptor alpha chain. |
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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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Interleukin-3 receptor in acute leukemia. |
Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C |
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PMID 14671644 |
IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease. |
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PMID 14500898 |
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 journal version : [ pdf ] [ DOI ] |
Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
del(X)(p22p22) P2RY8/CRLF2::del(Y)(p11p11) P2RY8/CRLF2
|
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
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