CD125 IL-5R α chain, CDw125
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Eosinophil
Basophil
B Cell
Mast Cell
60 / 60

Expression
CD125 is expressed on all B1 cells and by 2-4% of resting B-2 cells in the spleen.  CD125 is expressed on eosinophils, and basophils in the mouse and humans.  In the mouse, IL-5R is also expressed on mast cells and activated B cells.



Structure
MOLECULAR FAMILY NAME: Belongs to the hemopoietin superfamily.

CD125 is a single-pass type-1 a chain 399aa glycopeptide.  It contains a 322 aa extracellular domain which contains a N-terminal domain (similar to that found in CD116 and CD123) followed by a cytokine receptor domain (3 fibronectin-type-3 like modules) containing 4 cysteine residues in the 2nd module and the WSXWS motif in the 3rd module and 6 potential N-linked glycosylation sites, a 20 aa transmembrane domain and a 55 aa cytoplasmic domain which contains a proximal box 1 and a DC3 subregion, both of which are critical for signal transduction.  The IL-5R is formed by the association of CD125 and a common b chain CD131 that is also a component of the receptors for IL-3 and the granulocyte-macrophage colony-stimulating factor (GM-CSF).  CD125 is a cytokine receptor belonging to the hemopoietin receptor superfamily and the Ig gene superfamily.

MOLECULAR MASS
Cell Type Unreduced Reduced
Eosinophils 60 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Six alternative spliced transcripts variants yields 3 different isoforms.  Alternatively mRNA
splicing give rise a membrane bound form  and two soluble forms which exclude the last 3 exons that code for the transmembrane and cytoplasmic domains.

POST-TRANSLATIONAL MODIFICATION

There are 6 potential N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD125

CD125 binds IL-5R with a low affinity of kDa = 1 nM and when associated with CD131, binds IL-5 with high affinity of kDa = 50-250 pM.
 
Molecule Comment
IL-5
CD131 High affinity IL-5 receptor consists of CD125 and CD131

 

Function
CD125 is a IL-5 specific subunit of a heterodimeric cytokine receptor which is comprised of a ligand specific α subunit and a signal transducing β subunit shared by the receptors for CD123 (IL-3), colony stimulating factor 2 (CSF2/GM-CSF) and IL-5.  Binding of CD125 depends on the CD131 β subunit by the ligand binding and is required for the biological activities of IL-5.  It has been found to interact with syndecan binding protein (syntenin), which is required for IL-5 mediated activity of the transcription factor SOX4.  The box 1 motif of CD125 mediates activation of Bruton agammaglobulinaemia tyrosine kinase and the JAK2/STAT5 pathway and has been shown in vivo to be essential for IL-5 induced proliferation and differentiation of B-1 and CD125+ B-2 cells.  IL-5 mediated activation of CD125 plays a central role in eosinophil and basophil differentiation, functional activation and survival.  CD125 promotes the growth and differentiation of eosinophil precursors and activates mature eosinophils and is also a B cell growth and differentiation factor.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD125 IN INTACT ANIMAL

CD125 is a potential therapeutic target of eosinophilic inflammation is involved in the treatment of bronchial asthma and of allergic inflammatory conditions.  There is an impairment of B-1 cell development in IL-5Ra-deficient mice and there is an enhancement of survival of Angiostrongylus cantonensis in IL-5Ra-deficient mice.

Comments
In vivo administration of mAbs against the IL-5R inhibits eosinophilia in transgenic mice overexpressing IL-5R.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD125: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD125: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3568Q01344
MouseS12357P21183D90205
Antibodies

Revised June 25, 2008


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