P24394 (IL4RA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	825 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.9 Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. Ref.9
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.11 Ref.12 Ref.13 Ref.16
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.10 Ref.14 The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.10 Ref.14 The box 1 motif is required for JAK interaction and/or activation. Ref.10 Ref.14 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.10 Ref.14
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.13 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 process	Immunity
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Traceable author statement Ref.1. Source: ProtInc negative regulation of T-helper 1 cell differentiation Inferred from electronic annotation. Source: Compara ovulation Inferred from electronic annotation. Source: Compara positive regulation of T-helper 2 cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of chemokine secretion Inferred from electronic annotation. Source: Compara positive regulation of macrophage activation Inferred from electronic annotation. Source: Compara production of molecular mediator involved in inflammatory response Inferred from electronic annotation. Source: InterPro regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	interleukin-4 receptor activity Traceable author statement Ref.1. Source: ProtInc receptor signaling protein activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL4	P05112	5	EBI-367009,EBI-367025

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

By similarity

Chain

26 – 825

800

Interleukin-4 receptor subunit alpha

PRO_0000010887

Chain

26 – ?

Soluble interleukin-4 receptor subunit alpha

PRO_0000010888

Regions

Topological domain

26 – 232

207

Extracellular Potential

Transmembrane

233 – 256

24

Helical; Potential

Topological domain

257 – 825

569

Cytoplasmic Potential

Domain

123 – 219

97

Fibronectin type-III

Region

437 – 557

121

Required for IRS1 activation and IL4-induced cell growth

Region

558 – 657

100

Required for IL4-induced gene expression

Motif

212 – 216

5

WSXWS motif

Motif

262 – 270

9

Box 1 motif

Motif

711 – 716

6

ITIM motif

Compositional bias

370 – 380

11

Poly-Glu

Compositional bias

563 – 566

4

Poly-Ala

Compositional bias

789 – 794

6

Poly-Ser

Sites

Site

38

1

Major IL4 binding determinant

Site

64

1

Minor IL4 binding determinant

Site

66

1

Minor IL4 binding determinant

Site

92

1

Minor IL4 binding determinant

Site

94

1

Minor IL4 binding determinant

Site

97

1

Major IL4 binding determinant

Site

152

1

Minor IL4 binding determinant

Site

208

1

Major IL4 binding determinant

Amino acid modifications

Modified residue

497

1

Phosphotyrosine

Modified residue

575

1

Phosphotyrosine Probable

Modified residue

603

1

Phosphotyrosine Probable

Modified residue

631

1

Phosphotyrosine Probable

Glycosylation

53

1

N-linked (GlcNAc...) Potential

Glycosylation

98

1

N-linked (GlcNAc...) Potential

Glycosylation

128

1

N-linked (GlcNAc...) Potential

Glycosylation

134

1

N-linked (GlcNAc...) Potential

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Glycosylation

209

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 44

By similarity

Disulfide bond

74 ↔ 86

By similarity

Natural variations

Alternative sequence

225 – 227

3

YRE → NIC in isoform 2.

VSP_011116

Alternative sequence

228 – 825

598

Missing in isoform 2.

VSP_011117

Natural variant

75

1

I → F.
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].

VAR_059302

Natural variant

75

1

I → L.
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].

VAR_059303

Natural variant

75

1

I → V Associated with atopic asthma and cedar pollen sensitization. Ref.5 Ref.20 Ref.22 Ref.23 Ref.29
Corresponds to variant rs1805010 [ dbSNP | Ensembl ].

VAR_008034

Natural variant

387

1

S → L.
Corresponds to variant rs6413500 [ dbSNP | Ensembl ].

VAR_019999

Natural variant

400

1

E → A Associated with cedar pollen sensitization. Ref.5 Ref.8 Ref.20 Ref.29
Corresponds to variant rs1805011 [ dbSNP | Ensembl ].

VAR_011657

Natural variant

431

1

C → R. Ref.5 Ref.8 Ref.20
Corresponds to variant rs1805012 [ dbSNP | Ensembl ].

VAR_011658

Natural variant

436

1

S → L. Ref.5 Ref.8 Ref.20
Corresponds to variant rs1805013 [ dbSNP | Ensembl ].

VAR_011659

Natural variant

492

1

A → T.
Corresponds to variant rs35606110 [ dbSNP | Ensembl ].

VAR_049164

Natural variant

492

1

A → V.
Corresponds to variant rs34727572 [ dbSNP | Ensembl ].

VAR_049165

Natural variant

503

1

S → P Lowered total IgE concentration. Ref.5 Ref.8 Ref.24
Corresponds to variant rs1805015 [ dbSNP | Ensembl ].

VAR_011660

Natural variant

576

1

Q → R Associated with atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction. Ref.5 Ref.8 Ref.21 Ref.24 Ref.25 Ref.27
Corresponds to variant rs1801275 [ dbSNP | Ensembl ].

VAR_008035

Natural variant

579

1

V → I. Ref.5 Ref.8
Corresponds to variant rs3024677 [ dbSNP | Ensembl ].

VAR_011661

Natural variant

675

1

P → S. Ref.5
Corresponds to variant rs3024678 [ dbSNP | Ensembl ].

VAR_020000

Natural variant

752

1

S → A. Ref.5 Ref.26
Corresponds to variant rs1805016 [ dbSNP | Ensembl ].

VAR_011662

Natural variant

786

1

S → P in 1.8% of the population. Ref.20 Ref.28
Corresponds to variant rs1805014 [ dbSNP | Ensembl ].

VAR_011663

Experimental info

Mutagenesis

38

1

Y → A: 700-fold reduction in IL4 binding. Ref.17

Mutagenesis

38

1

Y → F: 25-fold reduction in IL4 binding. Ref.17

Mutagenesis

39

1

M → A: No effect on IL4 binding. Ref.17

Mutagenesis

40

1

S → A: No effect on IL4 binding. Ref.17

Mutagenesis

64

1

L → A: 100-fold reduction in IL4 binding. Ref.17

Mutagenesis

66

1

F → A: 45-fold reduction in IL4 binding. Ref.17

Mutagenesis

67

1

L → A: No effect on IL4 binding. Ref.17

Mutagenesis

68

1

L → A: No effect on IL4 binding. Ref.17

Mutagenesis

91

1

D → A: Little effect on IL4 binding. Ref.17

Mutagenesis

92

1

D → A: 50-fold reduction in IL4 binding. Ref.17

Mutagenesis

93

1

V → A: Little effect on IL4 binding. Ref.17

Mutagenesis

94

1

V → A: 35-fold reduction in IL4 binding. Ref.17

Mutagenesis

95

1

S → A: No effect on IL4 binding. Ref.17

Mutagenesis

97

1

D → A or N: >150-fold reduction in IL4 binding. Ref.17

Mutagenesis

98

1

N → A: No effect on IL4 binding. Ref.17

Mutagenesis

99

1

Y → A: 10-fold reduction in IL4 binding. Ref.17

Mutagenesis

116

1

K → A: Little effect on IL4 binding. Ref.17

Mutagenesis

117

1

P → A: Little effect on IL4 binding. Ref.17

Mutagenesis

118

1

S → A: No effect on IL4 binding. Ref.17

Mutagenesis

119

1

E → A: No effect on IL4 binding. Ref.17

Mutagenesis

150

1

D → A: Little effect on IL4 binding. Ref.17

Mutagenesis

151

1

N → A: Little effect on IL4 binding. Ref.17

Mutagenesis

152

1

Y → A: 40-fold reduction in IL4 binding. Ref.17

Mutagenesis

152

1

Y → F: No effect on IL4 binding. Ref.17

Mutagenesis

153

1

L → A: Little effect on IL4 binding. Ref.17

Mutagenesis

154

1

Y → A: Little effect on IL4 binding. Ref.17

Mutagenesis

208

1

Y → A: 500-fold reduction in IL4 binding. Ref.17

Mutagenesis

208

1

Y → F: 200-fold reduction in IL4 binding. Ref.17

Mutagenesis

497

1

Y → F: Abolishes IRS1 tyrosine phosphorylation. No cell proliferation. Ref.9

Mutagenesis

575

1

Y → F: Loss of CD23 gene induction; when associated with F-603 and F-631. Ref.14 Ref.25

Mutagenesis

603

1

Y → F: Loss of CD23 gene induction; when associated with F-575 and F-631. Ref.14

Mutagenesis

631

1

Y → F: Loss of CD23 gene induction; when associated with F-575 and F-603. Ref.14

Mutagenesis

713

1

Y → F: Increased IL4-induced cell proliferation and STAT6 activation. Ref.16

Secondary structure

1

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825

Helix Strand Turn

Details...

Beta strand

28 – 36

9

Beta strand

38 – 50

13

Helix

54 – 57

4

Beta strand

58 – 68

11

Beta strand

72 – 74

3

Beta strand

77 – 89

13

Beta strand

99 – 105

7

Beta strand

108 – 115

8

Helix

117 – 119

3

Beta strand

127 – 132

6

Turn

135 – 137

3

Beta strand

139 – 144

6

Helix

154 – 156

3

Beta strand

158 – 168

11

Beta strand

172 – 177

6

Beta strand

183 – 186

4

Helix

188 – 190

3

Beta strand

193 – 195

3

Beta strand

197 – 204

8

Helix

206 – 208

3

Beta strand

219 – 221

3

Helix

495 – 497

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Membrane-bound form) [UniParc]. Last modified March 1, 1992. Version 1. Checksum: 9F886DF5612297F8	FASTA	825	89,658
	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
	Isoform 2 (Soluble form) (sIL4Ralpha/splice) [UniParc]. Checksum: 9FE8FCC827717CC5	FASTA	227	25,553
	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 EPSLRIAAST LKSGISYRAR VRAWAQCYNT TWSEWSPSTK WHNSNIC

References

	« Hide 'large scale' referencesShow '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]	"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. , 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].
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
AC106739 Genomic DNA. No translation available.
BC151131 mRNA. Translation: AAI51132.1.
AJ293654 Genomic DNA. Translation: CAC20452.1.

IPI

IPI00444383.
IPI00444384.

PIR

A60386.

RefSeq

NP_000409.1. NM_000418.3.
NP_001244335.1. NM_001257406.1.
NP_001244336.1. NM_001257407.1.

UniGene

Hs.513457.
Hs.742121.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IAR	X-ray	2.30	B	27-232	[»]
1IRS	NMR	-	B	489-499	[»]
1ITE	model	-	C	26-232	[»]
3BPL	X-ray	2.93	B	27-227	[»]
3BPN	X-ray	3.02	B	27-227	[»]
3BPO	X-ray	3.00	B	27-227	[»]

ProteinModelPortal

P24394.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3223N.

IntAct

P24394. 7 interactions.

MINT

MINT-90363.

PTM databases

PhosphoSite

P24394.

Polymorphism databases

DMDM

124335.

Proteomic databases

PaxDb

P24394.

PRIDE

P24394.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000170630; ENSP00000170630; ENSG00000077238.
ENST00000395762; ENSP00000379111; ENSG00000077238.
ENST00000449195; ENSP00000410322; ENSG00000077238.
ENST00000543915; ENSP00000441667; ENSG00000077238.

GeneID

3566.

KEGG

hsa:3566.

UCSC

uc002dom.3. human.
uc002don.3. human.

Organism-specific databases

CTD

3566.

GeneCards

GC16P027325.

HGNC

HGNC:6015. IL4R.

HPA

CAB004451.

MIM

147781. gene.

neXtProt

NX_P24394.

PharmGKB

PA29832.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46569.

HOVERGEN

HBG052116.

InParanoid

P24394.

KO

K05071.

OMA

SPCCGCC.

OrthoDB

EOG4PG608.

PhylomeDB

P24394.

Enzyme and pathway databases

Pathway_Interaction_DB

il4_2pathway. IL4-mediated signaling events.

Gene expression databases

ArrayExpress

P24394.

Bgee

P24394.

Genevestigator

P24394.

GermOnline

ENSG00000077238. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR003961. Fibronectin_type3.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR013783. Ig-like_fold.
IPR015319. IL4Ra_N.
[Graphical view]

Pfam

PF09238. IL4Ra_N. 1 hit.
[Graphical view]

SMART

SM00060. FN3. 1 hit.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 2 hits.

PROSITE

PS50853. FN3. 1 hit.
PS01355. HEMATOPO_REC_S_F1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

IL4R. human.

EvolutionaryTrace

P24394.

GenomeRNAi

3566.

NextBio

13926.

SOURCE

Search...

Entry information

Entry name

IL4RA_HUMAN

Accession

Primary (citable) accession number: P24394
Secondary accession number(s): 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:	May 1, 2013
This is version 159 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.