IL3RA (Interleukin-3 Receptor alpha)

2005-05-01   Ugo Testa 

Department of Hematology, Oncology, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy

Identity

HGNC
LOCATION
Xp22.33
LOCUSID
ALIAS
CD123
FUSION GENES

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.

Proteins

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.

Implicated in

Bibliography

Pubmed IDLast YearTitleAuthors
125041252003Analysis of the 5' promoters for human IL-3 and GM-CSF receptor alpha genes.Akagawa E et al
150626472004Regulation of myeloid development and function by colony stimulating factors.Barreda DR et al
112073692001Structure 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.Carr PD et al
123844142002Identification of primary structural features that define the differential actions of IL-3 and GM-CSF receptors.Evans CA et al
109490312000Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival.Guthridge MA et al
24043371990Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.Itoh N et al
110217532000The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells.Jordan CT et al
18330641991Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors.Kitamura T et al
92784201997The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling.Klein BK et al
78879511995Structure of the gene encoding the alpha subunit of the human interleukin 3 receptor.Kosugi H et al
81007201993A cytokine receptor gene cluster in the X-Y pseudoautosomal region?Kremer E et al
82138381993Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.Milatovich A et al
111220832000Expression 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 et al
117263172001Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies.Muñoz L et al
153702012004Immunophenotypic features of acute myeloid leukemias overexpressing the interleukin 3 receptor alpha chain.Riccioni R et al
86494151996Human 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.Stomski FC et al
146716442004Interleukin-3 receptor in acute leukemia.Testa U et al
145008982003IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease.Wong S et al

Other Information

Locus ID:

NCBI: 3563
MIM: 430000
HGNC: 6012
Ensembl: ENSG00000185291

Variants:

dbSNP: 3563
ClinVar: 3563
TCGA: ENSG00000185291
COSMIC: IL3RA

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000185291ENST00000331035P26951
ENSG00000185291ENST00000381469P26951
ENSG00000185291ENST00000432757J3JS34

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
ApoptosisKEGGko04210
Jak-STAT signaling pathwayKEGGko04630
Hematopoietic cell lineageKEGGko04640
Cytokine-cytokine receptor interactionKEGGhsa04060
ApoptosisKEGGhsa04210
Jak-STAT signaling pathwayKEGGhsa04630
Hematopoietic cell lineageKEGGhsa04640
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
HemostasisREACTOMER-HSA-109582
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
GPVI-mediated activation cascadeREACTOMER-HSA-114604
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G-protein beta:gamma signallingREACTOMER-HSA-397795
G beta:gamma signalling through PI3KgammaREACTOMER-HSA-392451
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
RET signalingREACTOMER-HSA-8853659

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
240303782013T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia.111
175227112007Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia.93
175227112007Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia.93
197306832009The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.59
249274072014Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia.52
123514112002Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis.50
219338612011High levels of CD34+CD38low/-CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia: a Groupe Ouest-Est des Leucemies Aigues et Maladies du Sang (GOELAMS) study.46
206738682010A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM).36
204524822010Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.26
146716442004Interleukin-3 receptor in acute leukemia.22

Citation

Ugo Testa

IL3RA (Interleukin-3 Receptor alpha)

Atlas Genet Cytogenet Oncol Haematol. 2005-05-01

Online version: http://atlasgeneticsoncology.org/gene/40959/il3ra