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P24394 (IL4RA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-4 receptor subunit alpha

Short name=IL-4 receptor subunit alpha
Short name=IL-4R subunit alpha
Short name=IL-4R-alpha
Short name=IL-4RA
Alternative name(s):
CD_antigen=CD124

Cleaved into the following chain:

  1. Soluble interleukin-4 receptor subunit alpha
    Short name=Soluble IL-4 receptor subunit alpha
    Short name=Soluble IL-4R-alpha
    Short name=sIL4Ralpha/prot
    Alternative name(s):
    IL-4-binding protein
    Short name=IL4-BP
Gene names
Name:IL4R
Synonyms:IL4RA
ORF Names:582J2.1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length825 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. Ref.10

Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. Ref.10

Subunit structure

The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequent recruitment to the complex of the common gamma chain, in immune cells, creates a type I receptor and, in non-immune cells, of IL13RA1 forms a type II receptor. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor. Interacts with PIK3C3 By similarity. Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP By similarity. Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5; inhibits IL4 signaling By similarity. Ref.12 Ref.13 Ref.14 Ref.17

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Tissue specificity

Isoform 1 and isoform 2 are highly expressed in activated T-cells.

Domain

The extracellular domain represents the IL4 binding protein (IL4BP). Ref.11 Ref.15

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.11 Ref.15

The box 1 motif is required for JAK interaction and/or activation. Ref.11 Ref.15

Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Ref.11 Ref.15

Post-translational modification

On IL4 binding, phosphorylated on C-terminal tyrosine residues. Phosphorylation on any one of tyrosine residues, Tyr-575, Tyr-603 or Tyr-631, is required for STAT6-induced gene induction. Ref.14

The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase.

Polymorphism

Allelic variants in IL4RA are associated with a susceptibility to atopy, an immunological condition that can lead to clinical symptoms such as allergic rhinitis, sinusitis, asthma and eczema.

Allelic variants in IL4RA are associated with cedar pollen sensitization. Individuals develop Japanese cedar pollinosis with increased exposure to cedar pollen. Japanese cedar pollinosis is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 4 subfamily.

Contains 1 fibronectin type-III domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to protozoan

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement Ref.1. Source: ProtInc

interleukin-4-mediated signaling pathway

Traceable author statement Ref.1. Source: GOC

intracellular signal transduction

Traceable author statement Ref.1. Source: GOC

negative regulation of T-helper 1 cell differentiation

Inferred from electronic annotation. Source: Ensembl

ovulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 2 cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of macrophage activation

Inferred from electronic annotation. Source: Ensembl

production of molecular mediator involved in inflammatory response

Inferred from electronic annotation. Source: InterPro

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functioninterleukin-4 receptor activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction Ref.20PubMed 18243101PubMed 23597562PubMed 8266078PubMed 8816495Ref.22PubMed 9651359. Source: IntAct

receptor signaling protein activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P24394-1)

Also known as: Membrane-bound form;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P24394-2)

Also known as: Soluble form; sIL4Ralpha/splice;

The sequence of this isoform differs from the canonical sequence as follows:
     225-227: YRE → NIC
     228-825: Missing.
Isoform 3 (identifier: P24394-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MGWLCSGLLFPVSCLVLLQVASS → MQKDARRE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 By similarity
Chain26 – 825800Interleukin-4 receptor subunit alpha
PRO_0000010887
Chain26 – ?Soluble interleukin-4 receptor subunit alphaPRO_0000010888

Regions

Topological domain26 – 232207Extracellular Potential
Transmembrane233 – 25624Helical; Potential
Topological domain257 – 825569Cytoplasmic Potential
Domain125 – 224100Fibronectin type-III
Region437 – 557121Required for IRS1 activation and IL4-induced cell growth
Region558 – 657100Required for IL4-induced gene expression
Motif212 – 2165WSXWS motif
Motif262 – 2709Box 1 motif
Motif711 – 7166ITIM motif
Compositional bias370 – 38011Poly-Glu
Compositional bias563 – 5664Poly-Ala
Compositional bias789 – 7946Poly-Ser

Sites

Site381Major IL4 binding determinant
Site641Minor IL4 binding determinant
Site661Minor IL4 binding determinant
Site921Minor IL4 binding determinant
Site941Minor IL4 binding determinant
Site971Major IL4 binding determinant
Site1521Minor IL4 binding determinant
Site2081Major IL4 binding determinant

Amino acid modifications

Modified residue4971Phosphotyrosine
Modified residue5751Phosphotyrosine Probable
Modified residue6031Phosphotyrosine Probable
Modified residue6311Phosphotyrosine Probable
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation1281N-linked (GlcNAc...) Potential
Glycosylation1341N-linked (GlcNAc...) Potential
Glycosylation1761N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 44 By similarity
Disulfide bond74 ↔ 86 By similarity

Natural variations

Alternative sequence1 – 2323MGWLC…QVASS → MQKDARRE in isoform 3.
VSP_053738
Alternative sequence225 – 2273YRE → NIC in isoform 2.
VSP_011116
Alternative sequence228 – 825598Missing in isoform 2.
VSP_011117
Natural variant751I → F.
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
VAR_059302
Natural variant751I → L.
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
VAR_059303
Natural variant751I → V Associated with atopic asthma and cedar pollen sensitization. Ref.5 Ref.21 Ref.23 Ref.24 Ref.30
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
VAR_008034
Natural variant3871S → L.
Corresponds to variant rs6413500 [ dbSNP | Ensembl ].
VAR_019999
Natural variant4001E → A Associated with cedar pollen sensitization. Ref.5 Ref.9 Ref.21 Ref.30
Corresponds to variant rs1805011 [ dbSNP | Ensembl ].
VAR_011657
Natural variant4311C → R. Ref.5 Ref.9 Ref.21
Corresponds to variant rs1805012 [ dbSNP | Ensembl ].
VAR_011658
Natural variant4361S → L. Ref.5 Ref.9 Ref.21
Corresponds to variant rs1805013 [ dbSNP | Ensembl ].
VAR_011659
Natural variant4921A → T.
Corresponds to variant rs35606110 [ dbSNP | Ensembl ].
VAR_049164
Natural variant4921A → V.
Corresponds to variant rs34727572 [ dbSNP | Ensembl ].
VAR_049165
Natural variant5031S → P Lowered total IgE concentration. Ref.5 Ref.9 Ref.25
Corresponds to variant rs1805015 [ dbSNP | Ensembl ].
VAR_011660
Natural variant5761Q → R Associated with atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction. Ref.5 Ref.9 Ref.22 Ref.25 Ref.26 Ref.28
Corresponds to variant rs1801275 [ dbSNP | Ensembl ].
VAR_008035
Natural variant5791V → I. Ref.5 Ref.9
Corresponds to variant rs3024677 [ dbSNP | Ensembl ].
VAR_011661
Natural variant6751P → S. Ref.5
Corresponds to variant rs3024678 [ dbSNP | Ensembl ].
VAR_020000
Natural variant7521S → A. Ref.5 Ref.27
Corresponds to variant rs1805016 [ dbSNP | Ensembl ].
VAR_011662
Natural variant7861S → P in 1.8% of the population. Ref.21 Ref.29
Corresponds to variant rs1805014 [ dbSNP | Ensembl ].
VAR_011663

Experimental info

Mutagenesis381Y → A: 700-fold reduction in IL4 binding. Ref.18
Mutagenesis381Y → F: 25-fold reduction in IL4 binding. Ref.18
Mutagenesis391M → A: No effect on IL4 binding. Ref.18
Mutagenesis401S → A: No effect on IL4 binding. Ref.18
Mutagenesis641L → A: 100-fold reduction in IL4 binding. Ref.18
Mutagenesis661F → A: 45-fold reduction in IL4 binding. Ref.18
Mutagenesis671L → A: No effect on IL4 binding. Ref.18
Mutagenesis681L → A: No effect on IL4 binding. Ref.18
Mutagenesis911D → A: Little effect on IL4 binding. Ref.18
Mutagenesis921D → A: 50-fold reduction in IL4 binding. Ref.18
Mutagenesis931V → A: Little effect on IL4 binding. Ref.18
Mutagenesis941V → A: 35-fold reduction in IL4 binding. Ref.18
Mutagenesis951S → A: No effect on IL4 binding. Ref.18
Mutagenesis971D → A or N: >150-fold reduction in IL4 binding. Ref.18
Mutagenesis981N → A: No effect on IL4 binding. Ref.18
Mutagenesis991Y → A: 10-fold reduction in IL4 binding. Ref.18
Mutagenesis1161K → A: Little effect on IL4 binding. Ref.18
Mutagenesis1171P → A: Little effect on IL4 binding. Ref.18
Mutagenesis1181S → A: No effect on IL4 binding. Ref.18
Mutagenesis1191E → A: No effect on IL4 binding. Ref.18
Mutagenesis1501D → A: Little effect on IL4 binding. Ref.18
Mutagenesis1511N → A: Little effect on IL4 binding. Ref.18
Mutagenesis1521Y → A: 40-fold reduction in IL4 binding. Ref.18
Mutagenesis1521Y → F: No effect on IL4 binding. Ref.18
Mutagenesis1531L → A: Little effect on IL4 binding. Ref.18
Mutagenesis1541Y → A: Little effect on IL4 binding. Ref.18
Mutagenesis2081Y → A: 500-fold reduction in IL4 binding. Ref.18
Mutagenesis2081Y → F: 200-fold reduction in IL4 binding. Ref.18
Mutagenesis4971Y → F: Abolishes IRS1 tyrosine phosphorylation. No cell proliferation. Ref.10
Mutagenesis5751Y → F: Loss of CD23 gene induction; when associated with F-603 and F-631. Ref.15 Ref.26
Mutagenesis6031Y → F: Loss of CD23 gene induction; when associated with F-575 and F-631. Ref.15
Mutagenesis6311Y → F: Loss of CD23 gene induction; when associated with F-575 and F-603. Ref.15
Mutagenesis7131Y → F: Increased IL4-induced cell proliferation and STAT6 activation. Ref.17

Secondary structure

............................................ 825
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Membrane-bound form) [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: 9F886DF5612297F8

FASTA82589,658
        10         20         30         40         50         60 
MGWLCSGLLF PVSCLVLLQV ASSGNMKVLQ EPTCVSDYMS ISTCEWKMNG PTNCSTELRL 

        70         80         90        100        110        120 
LYQLVFLLSE AHTCIPENNG GAGCVCHLLM DDVVSADNYT LDLWAGQQLL WKGSFKPSEH 

       130        140        150        160        170        180 
VKPRAPGNLT VHTNVSDTLL LTWSNPYPPD NYLYNHLTYA VNIWSENDPA DFRIYNVTYL 

       190        200        210        220        230        240 
EPSLRIAAST LKSGISYRAR VRAWAQCYNT TWSEWSPSTK WHNSYREPFE QHLLLGVSVS 

       250        260        270        280        290        300 
CIVILAVCLL CYVSITKIKK EWWDQIPNPA RSRLVAIIIQ DAQGSQWEKR SRGQEPAKCP 

       310        320        330        340        350        360 
HWKNCLTKLL PCFLEHNMKR DEDPHKAAKE MPFQGSGKSA WCPVEISKTV LWPESISVVR 

       370        380        390        400        410        420 
CVELFEAPVE CEEEEEVEEE KGSFCASPES SRDDFQEGRE GIVARLTESL FLDLLGEENG 

       430        440        450        460        470        480 
GFCQQDMGES CLLPPSGSTS AHMPWDEFPS AGPKEAPPWG KEQPLHLEPS PPASPTQSPD 

       490        500        510        520        530        540 
NLTCTETPLV IAGNPAYRSF SNSLSQSPCP RELGPDPLLA RHLEEVEPEM PCVPQLSEPT 

       550        560        570        580        590        600 
TVPQPEPETW EQILRRNVLQ HGAAAAPVSA PTSGYQEFVH AVEQGGTQAS AVVGLGPPGE 

       610        620        630        640        650        660 
AGYKAFSSLL ASSAVSPEKC GFGASSGEEG YKPFQDLIPG CPGDPAPVPV PLFTFGLDRE 

       670        680        690        700        710        720 
PPRSPQSSHL PSSSPEHLGL EPGEKVEDMP KPPLPQEQAT DPLVDSLGSG IVYSALTCHL 

       730        740        750        760        770        780 
CGHLKQCHGQ EDGGQTPVMA SPCCGCCCGD RSSPPTTPLR APDPSPGGVP LEASLCPASL 

       790        800        810        820 
APSGISEKSK SSSSFHPAPG NAQSSSQTPK IVNFVSVGPT YMRVS 

« Hide

Isoform 2 (Soluble form) (sIL4Ralpha/splice) [UniParc].

Checksum: 9FE8FCC827717CC5
Show »

FASTA22725,553
Isoform 3 [UniParc].

Checksum: 234ADCAA655651CB
Show »

FASTA81088,267

References

« Hide 'large scale' references
[1]"Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily."
Idzerda R.L., March C.J., Mosley B., Lyman S.D., Bos T.V., Gimpel S.D., Din W.S., Grabstein K.H., Widmer M.B., Park L.S., Cosman D., Beckmann M.P.
J. Exp. Med. 171:861-873(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Peripheral blood.
[2]"Molecular cloning of a cDNA encoding the human interleukin 4 receptor."
Galizzi J.-P., Zuber C.E., Harada N., Gorman D.M., Djossou O., Kastelein R., Banchereau J., Howard M., Miyajima A.
Int. Immunol. 2:669-675(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Myeloid leukemia cell.
[3]"Characterization of the membrane-bound and a soluble form of human IL-4 receptor alpha produced by alternative splicing."
Kruse S., Forster J., Kuehr J., Deichmann K.A.
Int. Immunol. 11:1965-1970(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
Tissue: Blood.
[4]"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q."
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D.
Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
[5]SeattleSNPs variation discovery resource
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-75; ALA-400; ARG-431; LEU-436; PRO-503; ARG-576; ILE-579; SER-675 AND ALA-752.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Thymus.
[7]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[9]"Identification of a novel single-nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11."
Lozano F., Places L., Vila J.-M., Padilla O., Arman M., Gimferrer I., Suarez B., Lopez de la Iglesia A., Miserachs N., Vives J.
Tissue Antigens 57:216-220(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 301-825 (ISOFORM 1), VARIANTS ALA-400; ARG-431; LEU-436; PRO-503; ARG-576 AND ILE-579.
[10]"An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth."
Keegan A.D., Nelms K., White M., Wang L.-M., Pierce J.H., Paul W.E.
Cell 76:811-820(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IRS1 ACTIVATION, MUTAGENESIS OF TYR-497.
[11]"Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha."
Malabarba M.G., Kirken R.A., Rui H., Koettnitz K., Kawamura M., O'Shea J.J., Kalthoff F.S., Farrar W.L.
J. Biol. Chem. 270:9630-9637(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN JAK3 ACTIVATION.
[12]"The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor."
Zurawski S.M., Chomarat P., Djossou O., Bidaud C., McKenzie A.N., Miossec P., Banchereau J., Zurawski G.
J. Biol. Chem. 270:13869-13878(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL13RA1.
[13]"JAK3 associates with the human interleukin 4 receptor and is tyrosine phosphorylated following receptor triggering."
Rolling C., Treton D., Beckmann P., Galanaud P., Richard Y.
Oncogene 10:1757-1761(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JAK3.
[14]"IL4 and IL13 receptors share the gamma c chain and activate STAT6, STAT3 and STAT5 proteins in normal human B cells."
Rolling C., Treton D., Pellegrini S., Galanaud P., Richard Y.
FEBS Lett. 393:53-56(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL13RA1, PHOSPHORYLATION.
[15]"Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor."
Ryan J.J., McReynolds L.J., Keegan A., Wang L.-H., Garfein E., Rothman P., Nelms K., Paul W.E.
Immunity 4:123-132(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN STAT6 ACTIVATION, MUTAGENESIS OF TYR-575; TYR-603 AND TYR-631.
[16]"Soluble human interleukin-4 receptor is produced by activated T cells under the control of metalloproteinases."
Jung T., Schrader N., Hellwig M., Enssle K.H., Neumann C.
Int. Arch. Allergy Immunol. 119:23-30(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[17]"Immunoreceptor tyrosine-based inhibitory motif of the IL-4 receptor associates with SH2-containing phosphatases and regulates IL-4-induced proliferation."
Kashiwada M., Giallourakis C.C., Pan P.-Y., Rothman P.B.
J. Immunol. 167:6382-6387(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN6; PTPN11 AND INPP5D, STAT6 ACTIVATION, MUTAGENESIS OF TYR-713.
[18]"The high-affinity interaction of human IL-4 and the receptor alpha chain is constituted by two independent binding clusters."
Zhang J.-L., Simeonowa I., Wang Y., Sebald W.
J. Mol. Biol. 315:399-407(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: LIGAND-BINDING SITES, MUTAGENESIS OF TYR-38; MET-39; SER-40; LEU-64; PHE-66; LEU-67; LEU-68; ASP-91; ASP-92; VAL-93; VAL-94; SER-95; ASP-97; ASN-98; TYR-99; LYS-116; PRO-117; SER-118; GLU-119; ASP-150; ASN-151; TYR-152; LEU-153; TYR-154 AND TYR-208.
[19]"Regulation of the dephosphorylation of Stat6. Participation of Tyr-713 in the interleukin-4 receptor alpha, the tyrosine phosphatase SHP-1, and the proteasome."
Hanson E.M., Dickensheets H., Qu C.K., Donnelly R.P., Keegan A.D.
J. Biol. Chem. 278:3903-3911(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STAT6 ACTIVATION, INHIBITION BY TYROSINE PHOSPHATASE SHP1.
[20]"Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface."
Hage T., Sebald W., Reinemer P.
Cell 97:271-281(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-232 IN COMPLEX WITH IL4.
[21]"Common polymorphisms in the coding part of the IL4-receptor gene."
Deichmann K., Bardutzky J., Forster J., Heinzmann A., Kuehr J.
Biochem. Biophys. Res. Commun. 231:696-697(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-75; ALA-400; ARG-431; LEU-436 AND PRO-786.
[22]"The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor."
Hershey G.K.K., Friedrich M.F., Esswein L.A., Thomas M.L., Chatila T.A.
N. Engl. J. Med. 337:1720-1725(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-576.
[23]"Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma."
Mitsuyasu H., Izuhara K., Mao X.-Q., Gao P.S., Arinobu Y., Enomoto T., Kawai M., Sasaki S., Dake Y., Hamasaki N., Shirakawa T., Hopkin J.M.
Nat. Genet. 19:119-120(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-75.
[24]"No association between atopy/asthma and the Ile50Val polymorphism of IL-4 receptor."
Noguchi E., Shibasaki M., Arinami T., Takeda K., Yokouchi Y., Kobayashi K., Imoto N., Nakahara S., Matsui A., Hamaguchi H.
Am. J. Respir. Crit. Care Med. 160:342-345(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-75.
[25]"The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction."
Kruse S., Japha T., Tedner M., Sparholt S.H., Forster J., Kuehr J., Deichmann K.A.
Immunology 96:365-371(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRO-503 AND ARG-576.
[26]"Effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction."
Wang H.Y., Shelburne C.P., Zamorano J., Kelly A.E., Ryan J.J., Keegan A.D.
J. Immunol. 162:4385-4389(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT ARG-576, MUTAGENESIS OF TYR-575.
[27]"Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations."
Ober C., Leavitt S.A., Tsalenko A., Howard T.D., Hoki D.M., Daniel R., Newman D.L., Wu X., Parry R., Lester L.A., Solway J., Blumenthal M., King R.A., Xu J., Meyers D.A., Bleecker E.R., Cox N.J.
Am. J. Hum. Genet. 66:517-526(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-752.
[28]"Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan."
Oiso N., Fukai K., Ishii M.
Br. J. Dermatol. 142:1003-1006(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-576.
[29]"Analysis of the Ser786Pro interleukin-4 receptor alpha allelic variant in allergic and nonallergic asthma and its functional consequences."
Andrews R.P., Burrell L., Rosa-Rosa L., Cunningham C.M., Brzezinski J.L., Bernstein J.A., Khurana Hershey G.K.
Clin. Immunol. 100:298-304(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-786.
[30]"High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis."
Nakamura H., Miyagawa K., Ogino K., Endo T., Imai T., Ozasa K., Motohashi Y., Matsuzaki I., Sasahara S., Hatta K., Eboshida A.
J. Allergy Clin. Immunol. 112:1127-1131(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-75 AND ALA-400, POLYMORPHISM.
+Additional computationally mapped references.

Web resources

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52425 mRNA. Translation: CAA36672.1.
AC004525 Genomic DNA. Translation: AAC23495.1.
AF421855 Genomic DNA. Translation: AAL12163.1.
AJ293647 Genomic DNA. Translation: CAC20445.1.
AJ293648 Genomic DNA. Translation: CAC20446.1.
AJ293649 Genomic DNA. Translation: CAC20447.1.
AJ293650 Genomic DNA. Translation: CAC20448.1.
AJ293651 Genomic DNA. Translation: CAC20449.1.
AJ293652 Genomic DNA. Translation: CAC20450.1.
AJ293653 Genomic DNA. Translation: CAC20451.1.
AK303255 mRNA. Translation: BAG64338.1.
AC106739 Genomic DNA. No translation available.
BC151131 mRNA. Translation: AAI51132.1.
AJ293654 Genomic DNA. Translation: CAC20452.1.
CCDSCCDS10629.1. [P24394-1]
PIRA60386.
RefSeqNP_000409.1. NM_000418.3. [P24394-1]
NP_001244335.1. NM_001257406.1. [P24394-1]
NP_001244336.1. NM_001257407.1. [P24394-3]
UniGeneHs.513457.
Hs.742121.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IARX-ray2.30B26-232[»]
1IRSNMR-B489-499[»]
1ITEmodel-C26-232[»]
3BPLX-ray2.93B27-227[»]
3BPNX-ray3.02B27-227[»]
3BPOX-ray3.00B27-227[»]
ProteinModelPortalP24394.
SMRP24394. Positions 27-224.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109780. 18 interactions.
DIPDIP-3223N.
IntActP24394. 10 interactions.
MINTMINT-90363.

PTM databases

PhosphoSiteP24394.

Polymorphism databases

DMDM124335.

Proteomic databases

PaxDbP24394.
PRIDEP24394.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000170630; ENSP00000170630; ENSG00000077238. [P24394-1]
ENST00000380922; ENSP00000370309; ENSG00000077238. [P24394-3]
ENST00000395762; ENSP00000379111; ENSG00000077238. [P24394-1]
ENST00000449195; ENSP00000410322; ENSG00000077238. [P24394-2]
ENST00000543915; ENSP00000441667; ENSG00000077238. [P24394-1]
GeneID3566.
KEGGhsa:3566.
UCSCuc002don.4. human. [P24394-1]

Organism-specific databases

CTD3566.
GeneCardsGC16P027325.
HGNCHGNC:6015. IL4R.
HPACAB004451.
HPA050124.
MIM147781. gene.
neXtProtNX_P24394.
PharmGKBPA29832.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46569.
HOVERGENHBG052116.
InParanoidP24394.
KOK05071.
OMASPCCGCC.
OrthoDBEOG73RBCJ.
PhylomeDBP24394.
TreeFamTF337996.

Enzyme and pathway databases

SignaLinkP24394.

Gene expression databases

ArrayExpressP24394.
BgeeP24394.
GenevestigatorP24394.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR003961. Fibronectin_type3.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR013783. Ig-like_fold.
IPR015319. IL-4_rcpt-alpha_N.
[Graphical view]
PfamPF09238. IL4Ra_N. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01355. HEMATOPO_REC_S_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIL4R. human.
EvolutionaryTraceP24394.
GeneWikiInterleukin-4_receptor.
GenomeRNAi3566.
NextBio13926.
PROP24394.
SOURCESearch...

Entry information

Entry nameIL4RA_HUMAN
AccessionPrimary (citable) accession number: P24394
Secondary accession number(s): B4E076 expand/collapse secondary AC list , B9EKU8, H3BSY5, Q96P01, Q9H181, Q9H182, Q9H183, Q9H184, Q9H185, Q9H186, Q9H187, Q9H188
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 172 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries