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P24394

- IL4RA_HUMAN

UniProt

P24394 - IL4RA_HUMAN

Protein

Interleukin-4 receptor subunit alpha

Gene

IL4R

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 174 (01 Oct 2014)
      Sequence version 1 (01 Mar 1992)
      Previous versions | rss
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    Functioni

    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/IRS2.1 Publication
    Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei38 – 381Major IL4 binding determinant
    Sitei64 – 641Minor IL4 binding determinant
    Sitei66 – 661Minor IL4 binding determinant
    Sitei92 – 921Minor IL4 binding determinant
    Sitei94 – 941Minor IL4 binding determinant
    Sitei97 – 971Major IL4 binding determinant
    Sitei152 – 1521Minor IL4 binding determinant
    Sitei208 – 2081Major IL4 binding determinant

    GO - Molecular functioni

    1. interleukin-4 receptor activity Source: ProtInc
    2. protein binding Source: IntAct
    3. receptor signaling protein activity Source: ProtInc

    GO - Biological processi

    1. defense response to protozoan Source: Ensembl
    2. immune response Source: ProtInc
    3. interleukin-4-mediated signaling pathway Source: GOC
    4. intracellular signal transduction Source: GOC
    5. negative regulation of T-helper 1 cell differentiation Source: Ensembl
    6. ovulation Source: Ensembl
    7. positive regulation of chemokine secretion Source: Ensembl
    8. positive regulation of macrophage activation Source: Ensembl
    9. positive regulation of T-helper 2 cell differentiation Source: Ensembl
    10. production of molecular mediator involved in inflammatory response Source: InterPro
    11. regulation of cell proliferation Source: Ensembl
    12. response to estrogen Source: Ensembl
    13. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Immunity

    Enzyme and pathway databases

    SignaLinkiP24394.

    Names & Taxonomyi

    Protein namesi
    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:
    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 namesi
    Name:IL4R
    Synonyms:IL4RA
    ORF Names:582J2.1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:6015. IL4R.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular space Source: Ensembl
    2. integral component of plasma membrane Source: ProtInc
    3. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi38 – 381Y → A: 700-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi38 – 381Y → F: 25-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi39 – 391M → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi40 – 401S → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi64 – 641L → A: 100-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi66 – 661F → A: 45-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi67 – 671L → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi68 – 681L → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi91 – 911D → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi92 – 921D → A: 50-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi93 – 931V → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi94 – 941V → A: 35-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi95 – 951S → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi97 – 971D → A or N: >150-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi98 – 981N → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi99 – 991Y → A: 10-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi116 – 1161K → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi117 – 1171P → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi118 – 1181S → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi119 – 1191E → A: No effect on IL4 binding. 1 Publication
    Mutagenesisi150 – 1501D → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi151 – 1511N → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi152 – 1521Y → A: 40-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi152 – 1521Y → F: No effect on IL4 binding. 1 Publication
    Mutagenesisi153 – 1531L → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi154 – 1541Y → A: Little effect on IL4 binding. 1 Publication
    Mutagenesisi208 – 2081Y → A: 500-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi208 – 2081Y → F: 200-fold reduction in IL4 binding. 1 Publication
    Mutagenesisi497 – 4971Y → F: Abolishes IRS1 tyrosine phosphorylation. No cell proliferation. 1 Publication
    Mutagenesisi575 – 5751Y → F: Loss of CD23 gene induction; when associated with F-603 and F-631. 2 Publications
    Mutagenesisi603 – 6031Y → F: Loss of CD23 gene induction; when associated with F-575 and F-631. 1 Publication
    Mutagenesisi631 – 6311Y → F: Loss of CD23 gene induction; when associated with F-575 and F-603. 1 Publication
    Mutagenesisi713 – 7131Y → F: Increased IL4-induced cell proliferation and STAT6 activation. 1 Publication

    Organism-specific databases

    PharmGKBiPA29832.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525By similarityAdd
    BLAST
    Chaini26 – 825800Interleukin-4 receptor subunit alphaPRO_0000010887Add
    BLAST
    Chaini26 – ?Soluble interleukin-4 receptor subunit alphaPRO_0000010888

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi34 ↔ 44By similarity
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi74 ↔ 86By similarity
    Glycosylationi98 – 981N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi128 – 1281N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi209 – 2091N-linked (GlcNAc...)Sequence Analysis
    Modified residuei497 – 4971Phosphotyrosine1 Publication
    Modified residuei575 – 5751Phosphotyrosine1 Publication
    Modified residuei603 – 6031Phosphotyrosine1 Publication
    Modified residuei631 – 6311Phosphotyrosine1 Publication

    Post-translational modificationi

    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.1 Publication
    The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP24394.
    PRIDEiP24394.

    PTM databases

    PhosphoSiteiP24394.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiP24394.
    BgeeiP24394.
    GenevestigatoriP24394.

    Organism-specific databases

    HPAiCAB004451.
    HPA050124.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IL4P051127EBI-367009,EBI-367025
    STAT6P422264EBI-367009,EBI-1186478

    Protein-protein interaction databases

    BioGridi109780. 18 interactions.
    DIPiDIP-3223N.
    IntActiP24394. 10 interactions.
    MINTiMINT-90363.

    Structurei

    Secondary structure

    1
    825
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi28 – 369
    Beta strandi38 – 5013
    Helixi54 – 574
    Beta strandi58 – 6811
    Beta strandi72 – 743
    Beta strandi77 – 8913
    Beta strandi99 – 1057
    Beta strandi108 – 1158
    Helixi117 – 1193
    Beta strandi127 – 1326
    Turni135 – 1373
    Beta strandi139 – 1446
    Helixi154 – 1563
    Beta strandi158 – 16811
    Beta strandi172 – 1776
    Beta strandi183 – 1864
    Helixi188 – 1903
    Beta strandi193 – 1953
    Beta strandi197 – 2048
    Helixi206 – 2083
    Beta strandi219 – 2213
    Helixi495 – 4973

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP24394.
    SMRiP24394. Positions 27-224.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP24394.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini26 – 232207ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini257 – 825569CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei233 – 25624HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini125 – 224100Fibronectin type-IIIPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni437 – 557121Required for IRS1 activation and IL4-induced cell growthAdd
    BLAST
    Regioni558 – 657100Required for IL4-induced gene expressionAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi212 – 2165WSXWS motif
    Motifi262 – 2709Box 1 motif
    Motifi711 – 7166ITIM motif

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi370 – 38011Poly-GluAdd
    BLAST
    Compositional biasi563 – 5664Poly-Ala
    Compositional biasi789 – 7946Poly-Ser

    Domaini

    The extracellular domain represents the IL4 binding protein (IL4BP).
    The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
    The box 1 motif is required for JAK interaction and/or activation.

    Sequence similaritiesi

    Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG46569.
    HOVERGENiHBG052116.
    InParanoidiP24394.
    KOiK05071.
    OMAiSPCCGCC.
    OrthoDBiEOG73RBCJ.
    PhylomeDBiP24394.
    TreeFamiTF337996.

    Family and domain databases

    Gene3Di2.60.40.10. 2 hits.
    InterProiIPR003961. Fibronectin_type3.
    IPR003531. Hempt_rcpt_S_F1_CS.
    IPR013783. Ig-like_fold.
    IPR015319. IL-4_rcpt-alpha_N.
    [Graphical view]
    PfamiPF09238. IL4Ra_N. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 2 hits.
    PROSITEiPS50853. FN3. 1 hit.
    PS01355. HEMATOPO_REC_S_F1. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P24394-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MGWLCSGLLF PVSCLVLLQV ASSGNMKVLQ EPTCVSDYMS ISTCEWKMNG    50
    PTNCSTELRL LYQLVFLLSE AHTCIPENNG GAGCVCHLLM DDVVSADNYT 100
    LDLWAGQQLL WKGSFKPSEH VKPRAPGNLT VHTNVSDTLL LTWSNPYPPD 150
    NYLYNHLTYA VNIWSENDPA DFRIYNVTYL EPSLRIAAST LKSGISYRAR 200
    VRAWAQCYNT TWSEWSPSTK WHNSYREPFE QHLLLGVSVS CIVILAVCLL 250
    CYVSITKIKK EWWDQIPNPA RSRLVAIIIQ DAQGSQWEKR SRGQEPAKCP 300
    HWKNCLTKLL PCFLEHNMKR DEDPHKAAKE MPFQGSGKSA WCPVEISKTV 350
    LWPESISVVR CVELFEAPVE CEEEEEVEEE KGSFCASPES SRDDFQEGRE 400
    GIVARLTESL FLDLLGEENG GFCQQDMGES CLLPPSGSTS AHMPWDEFPS 450
    AGPKEAPPWG KEQPLHLEPS PPASPTQSPD NLTCTETPLV IAGNPAYRSF 500
    SNSLSQSPCP RELGPDPLLA RHLEEVEPEM PCVPQLSEPT TVPQPEPETW 550
    EQILRRNVLQ HGAAAAPVSA PTSGYQEFVH AVEQGGTQAS AVVGLGPPGE 600
    AGYKAFSSLL ASSAVSPEKC GFGASSGEEG YKPFQDLIPG CPGDPAPVPV 650
    PLFTFGLDRE PPRSPQSSHL PSSSPEHLGL EPGEKVEDMP KPPLPQEQAT 700
    DPLVDSLGSG IVYSALTCHL CGHLKQCHGQ EDGGQTPVMA SPCCGCCCGD 750
    RSSPPTTPLR APDPSPGGVP LEASLCPASL APSGISEKSK SSSSFHPAPG 800
    NAQSSSQTPK IVNFVSVGPT YMRVS 825
    Length:825
    Mass (Da):89,658
    Last modified:March 1, 1992 - v1
    Checksum:i9F886DF5612297F8
    GO
    Isoform 2 (identifier: P24394-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:227
    Mass (Da):25,553
    Checksum:i9FE8FCC827717CC5
    GO
    Isoform 3 (identifier: P24394-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-23: MGWLCSGLLFPVSCLVLLQVASS → MQKDARRE

    Note: No experimental confirmation available.

    Show »
    Length:810
    Mass (Da):88,267
    Checksum:i234ADCAA655651CB
    GO

    Polymorphismi

    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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti75 – 751I → F.
    Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
    VAR_059302
    Natural varianti75 – 751I → L.
    Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
    VAR_059303
    Natural varianti75 – 751I → V Associated with atopic asthma and cedar pollen sensitization. 5 Publications
    Corresponds to variant rs1805010 [ dbSNP | Ensembl ].
    VAR_008034
    Natural varianti387 – 3871S → L.
    Corresponds to variant rs6413500 [ dbSNP | Ensembl ].
    VAR_019999
    Natural varianti400 – 4001E → A Associated with cedar pollen sensitization. 4 Publications
    Corresponds to variant rs1805011 [ dbSNP | Ensembl ].
    VAR_011657
    Natural varianti431 – 4311C → R.3 Publications
    Corresponds to variant rs1805012 [ dbSNP | Ensembl ].
    VAR_011658
    Natural varianti436 – 4361S → L.3 Publications
    Corresponds to variant rs1805013 [ dbSNP | Ensembl ].
    VAR_011659
    Natural varianti492 – 4921A → T.
    Corresponds to variant rs35606110 [ dbSNP | Ensembl ].
    VAR_049164
    Natural varianti492 – 4921A → V.
    Corresponds to variant rs34727572 [ dbSNP | Ensembl ].
    VAR_049165
    Natural varianti503 – 5031S → P Lowered total IgE concentration. 3 Publications
    Corresponds to variant rs1805015 [ dbSNP | Ensembl ].
    VAR_011660
    Natural varianti576 – 5761Q → R Associated with atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction. 5 Publications
    Corresponds to variant rs1801275 [ dbSNP | Ensembl ].
    VAR_008035
    Natural varianti579 – 5791V → I.2 Publications
    Corresponds to variant rs3024677 [ dbSNP | Ensembl ].
    VAR_011661
    Natural varianti675 – 6751P → S.1 Publication
    Corresponds to variant rs3024678 [ dbSNP | Ensembl ].
    VAR_020000
    Natural varianti752 – 7521S → A.2 Publications
    Corresponds to variant rs1805016 [ dbSNP | Ensembl ].
    VAR_011662
    Natural varianti786 – 7861S → P in 1.8% of the population. 2 Publications
    Corresponds to variant rs1805014 [ dbSNP | Ensembl ].
    VAR_011663

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2323MGWLC…QVASS → MQKDARRE in isoform 3. 1 PublicationVSP_053738Add
    BLAST
    Alternative sequencei225 – 2273YRE → NIC in isoform 2. CuratedVSP_011116
    Alternative sequencei228 – 825598Missing in isoform 2. CuratedVSP_011117Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS10629.1. [P24394-1]
    CCDS58441.1. [P24394-3]
    PIRiA60386.
    RefSeqiNP_000409.1. NM_000418.3. [P24394-1]
    NP_001244335.1. NM_001257406.1. [P24394-1]
    NP_001244336.1. NM_001257407.1. [P24394-3]
    UniGeneiHs.513457.
    Hs.742121.

    Genome annotation databases

    EnsembliENST00000170630; ENSP00000170630; ENSG00000077238. [P24394-1]
    ENST00000395762; ENSP00000379111; ENSG00000077238. [P24394-1]
    ENST00000543915; ENSP00000441667; ENSG00000077238. [P24394-1]
    GeneIDi3566.
    KEGGihsa:3566.
    UCSCiuc002don.4. human. [P24394-1]

    Polymorphism databases

    DMDMi124335.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs
    SHMPD

    The Singapore human mutation and polymorphism database

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS10629.1. [P24394-1 ]
    CCDS58441.1. [P24394-3 ]
    PIRi A60386.
    RefSeqi NP_000409.1. NM_000418.3. [P24394-1 ]
    NP_001244335.1. NM_001257406.1. [P24394-1 ]
    NP_001244336.1. NM_001257407.1. [P24394-3 ]
    UniGenei Hs.513457.
    Hs.742121.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IAR X-ray 2.30 B 26-232 [» ]
    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 [» ]
    ProteinModelPortali P24394.
    SMRi P24394. Positions 27-224.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109780. 18 interactions.
    DIPi DIP-3223N.
    IntActi P24394. 10 interactions.
    MINTi MINT-90363.

    PTM databases

    PhosphoSitei P24394.

    Polymorphism databases

    DMDMi 124335.

    Proteomic databases

    PaxDbi P24394.
    PRIDEi P24394.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000170630 ; ENSP00000170630 ; ENSG00000077238 . [P24394-1 ]
    ENST00000395762 ; ENSP00000379111 ; ENSG00000077238 . [P24394-1 ]
    ENST00000543915 ; ENSP00000441667 ; ENSG00000077238 . [P24394-1 ]
    GeneIDi 3566.
    KEGGi hsa:3566.
    UCSCi uc002don.4. human. [P24394-1 ]

    Organism-specific databases

    CTDi 3566.
    GeneCardsi GC16P027325.
    HGNCi HGNC:6015. IL4R.
    HPAi CAB004451.
    HPA050124.
    MIMi 147781. gene.
    neXtProti NX_P24394.
    PharmGKBi PA29832.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46569.
    HOVERGENi HBG052116.
    InParanoidi P24394.
    KOi K05071.
    OMAi SPCCGCC.
    OrthoDBi EOG73RBCJ.
    PhylomeDBi P24394.
    TreeFami TF337996.

    Enzyme and pathway databases

    SignaLinki P24394.

    Miscellaneous databases

    ChiTaRSi IL4R. human.
    EvolutionaryTracei P24394.
    GeneWikii Interleukin-4_receptor.
    GenomeRNAii 3566.
    NextBioi 13926.
    PROi P24394.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P24394.
    Bgeei P24394.
    Genevestigatori P24394.

    Family and domain databases

    Gene3Di 2.60.40.10. 2 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR003531. Hempt_rcpt_S_F1_CS.
    IPR013783. Ig-like_fold.
    IPR015319. IL-4_rcpt-alpha_N.
    [Graphical view ]
    Pfami PF09238. IL4Ra_N. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 2 hits.
    PROSITEi PS50853. FN3. 1 hit.
    PS01355. HEMATOPO_REC_S_F1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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.
      , 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.
      , 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. 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.

    Entry informationi

    Entry nameiIL4RA_HUMAN
    AccessioniPrimary (citable) accession number: P24394
    Secondary accession number(s): B4E076
    , B9EKU8, H3BSY5, Q96P01, Q9H181, Q9H182, Q9H183, Q9H184, Q9H185, Q9H186, Q9H187, Q9H188
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 1992
    Last sequence update: March 1, 1992
    Last modified: October 1, 2014
    This is version 174 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3