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CD124; interleukin-4 receptor alpha chain; IL-4R-alpha; sIL4Ralpha/prot; IL-4-binding protein; IL4-BP (IL4R, 582J21, IL4RA)

Function: - subunit for both IL-4 receptor & IL-13 receptor - couples to the JAK1/2/3-STAT6 pathway - soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation & IL5 up-regulation by T-cells - interacts with the IL13/IL13RA1 complex to form a type 2 receptor - interacts with PIK3C3 (putative) - interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 & INPP5D/SHIP (putative) - interacts with JAK1 through a Box 1-containing region - in Th1 cells, binds N-terminal 50 amino acids of SOCS5, which inhibits JAK1 interaction, STAT6 activation & Th2 cell differentiation - SOCS5 interaction is independent of Tur phosphorylation (putative) - on IL4 binding, phosphorylated on C-terminal Tyr. - phosphorylation on any one of Tyr-575, Tyr-603 or Tyr-631, is required for STAT6-induced gene induction - the soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase Structure: - the extracellular domain represents the IL4 binding protein (IL4BP) - the WSXWS motif appears to be necessary for proper protein folding, efficient intracellular transport & cell-surface receptor binding - the box 1 motif is required for JAK interaction &/or activation - contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM) - phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases - belongs to the type I cytokine receptor family, type 4 subfamily - contains 1 fibronectin F3 module Compartment: - cell membrane - isoform 2: secreted Alternative splicing: named isoforms=2 Expression: - both isoform 1 & isoform 2 are highly expressed in activated T-cells Pathology: - allelic variants in IL4RA are associated with a susceptibility to atopy

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein hematopoietin receptor superfamily phosphoprotein

Properties

SIZE: entity length = 825 aa MW = 90 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-25} cysteine residue {C34} MODIFICATION: cysteine residue {C44} tyrosine residue {38} cysteine residue {C44} MODIFICATION: cysteine residue {C34} N-glycosylation site {N53} leucine residue {64} phenylalanine residue {66} cysteine residue {C74} MODIFICATION: cysteine residue {C86} cysteine residue {C86} MODIFICATION: cysteine residue {C74} aspartate residue {92} valine residue {94} aspartate residue {97} N-glycosylation site {N98} fibronectin type III domain or F3 module {123-219} MOTIF: N-glycosylation site {N128} N-glycosylation site {N134} tyrosine residue {152} N-glycosylation site {N176} tyrosine residue {208} N-glycosylation site {N209} WSXWS motif {212-216} transmembrane domain {233-256} box1 motif SITE: 262-270 FOR-BINDING-OF: Janus kinase (JAK) glutamate-rich region {370-380} MOTIF: glutamate residue (SEVERAL) IRS1 activation {437-557} MOTIF: Tyr phosphorylation site {Y497} IL4 expression {558-657} MOTIF: alanine-rich region {563-566} MOTIF: alanine residue (SEVERAL) Tyr phosphorylation site {Y575} Tyr phosphorylation site {Y603} Tyr phosphorylation site {Y631} immunoreceptor tyrosine-based inhibitory motif (ITIM) {711-716} serine-rich region {789-794} MOTIF: serine residue (SEVERAL)

Database Correlations

OMIM 147781 MORBIDMAP 147781 UniProt P24394 Pfam PF09238 Kegg hsa:3566

References

  1. UniProt :accession P24394
  2. SeattleSNPs http://pga.gs.washington.edu/data/il4r/
  3. SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=IL4R
  4. Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: 8048164
  5. Klaus GG, Harnett MM. Cross-talk between B cell surface immunoglobulin and interleukin 4 receptors: the role of protein kinase C and Ca2(+)-mediated signals. Eur J Immunol. 1990 Oct;20(10):2301-7. PMID: 2173663
  6. Taga T & Kishimoto T Cytokine receptors and signal transduction FASEB J 6:3387 1992 PMID: 1334470
  7. Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: 8048164

Component-of

interleukin-4 receptor (IL4 receptor)