IL3RA (Interleukin-3 Receptor alpha)

Identity

Other names	CD123
HGNC	IL3RA
Location	Yp13.3
Location_base_pair	Starts at 1415509 and ends at 1461582 bp from pter ( according to or).

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	IL3RA   6012
Entrez_Gene	IL3RA  3563  interleukin 3 receptor, alpha (low affinity)
	Cards
Atlas	IL3RAID40959chXp22Yp13
GeneCards	IL3RA
Ensembl	IL3RA [Search_View]   ENSG00000185291 [Gene_View]  IL3RA [Vega]
Genatlas	IL3RA
GeneLynx	IL3RA
eGenome	IL3RA
euGene	3563
	Genomic and cartography
GoldenPath	IL3RA  -  Yp13.3   chrX:1415509-1461582 +  Xp22.3   [Description]    (or)
Ensembl	IL3RA - Xp22.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	IL3RA
	Gene and transcription
Genbank	AK290568 [ ENTREZ ]
Genbank	AW452270 [ ENTREZ ]
Genbank	BC035407 [ ENTREZ ]
Genbank	EU176623 [ ENTREZ ]
Genbank	M74782 [ ENTREZ ]
RefSeq	NM_002183 [ SRS ]    NM_002183 [ ENTREZ ]
RefSeq	NC_000023 [ SRS ]    NC_000023 [ ENTREZ ]
RefSeq	NC_000024 [ SRS ]    NC_000024 [ ENTREZ ]
RefSeq	NT_033330 [ SRS ]    NT_033330 [ ENTREZ ]
RefSeq	NT_113972 [ SRS ]    NT_113972 [ ENTREZ ]
RefSeq	NW_001841157 [ SRS ]    NW_001841157 [ ENTREZ ]
CCDS	IL3RA CCDS - NCBI
AceView	IL3RA AceView - NCBI
Unigene	Hs.632790 [ SRS ]    Hs.632790 [ NCBI ]     HS632790 [ spliceNest ]
Fast-db	905 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P26951 [ SRS]    P26951 [ EXPASY ]     P26951 [ INTERPRO ]     P26951 [ UNIPROT ] P26951 [ VarSplice ]
Prosite	PS01356 HEMATOPO_REC_S_F2 [ SRS ]    PS01356 HEMATOPO_REC_S_F2 [ Expasy ]
Interpro	IPR008957 Fibronectin_typ-III-like_fold [ SRS ]    IPR008957 Fibronectin_typ-III-like_fold [ EBI ]
Interpro	IPR003532 Hempt_rcpt_S_F2_CS [ SRS ]    IPR003532 Hempt_rcpt_S_F2_CS [ EBI ]
CluSTr	P26951
Blocks	P26951
HPRD	02392
	Protein Interaction databases
DIP	P26951
IntAct	P26951
	Polymorphism : SNP, mutations, diseases
OMIM	308385;430000    [ map ]
GENECLINICS	308385;430000
SNP	IL3RA [dbSNP-NCBI]
SNP	NM_002183 [SNP-NCI]
SNP	IL3RA [GeneSNPs - Utah]  IL3RA] [HGBASE - SRS]
HAPMAP	IL3RA [HAPMAP]
COSMIC	IL3RA [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	IL3RA
Genetic Association	IL3RA
CDC HuGE	IL3RA
	General knowledge
Family Browser	IL3RA [UCSC Family Browser]
SOURCE	NM_002183
SMD	Hs.632790
SAGE	Hs.632790
GO	receptor activity [Amigo]  receptor activity
GO	hematopoietin/interferon-class (D200-domain) cytokine receptor activity [Amigo]  hematopoietin/interferon-class (D200-domain) cytokine receptor activity
GO	interleukin-3 receptor activity [Amigo]  interleukin-3 receptor activity
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
BIOCARTA	Regulation of BAD phosphorylation    [Genes]
BIOCARTA	IL 3 signaling pathway    [Genes]
KEGG	Cytokine-cytokine receptor interaction
KEGG	Apoptosis
KEGG	Jak-STAT signaling pathway
KEGG	Hematopoietic cell lineage
PubGene	IL3RA
TreeFam	IL3RA
CTD	3563 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	IL3RA Related clones (RZPD - Berlin)
	PubMed
PubMed	33 Pubmed reference(s) in Entrez

Bibliography

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PMID 1833064

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PMID 8100720

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PMID 8213838

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PMID 7887951

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PMID 8649415

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PMID 9278420

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.

Guthridge MA, Stomski FC, Barry EF, Winnall W, Woodcock JM, McClure BJ, Dottore M, Berndt MC, Lopez AF

Molecular cell. 2000 ; 6 (1) : 99-108.

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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Blood. 2002 ; 100 (9) : 3164-3174.

PMID 12384414

Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis.

Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P, Latagliata R, Mariani G, Rossini A, Battistini A, Lo-Coco F, Peschle C

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PMID 12351411

Analysis of the 5' promoters for human IL-3 and GM-CSF receptor alpha genes.

Akagawa E, Muto A, Arai K, Watanabe S

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

Leukemia & lymphoma. 2004 ; 45 (8) : 1511-1517.

PMID 15370201

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

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Last year publications	automatic search in PubMed

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Contributor(s)

Written	05-2005	Ugo 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sun Nov 9 19:42:05 2008