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Protein

Interleukin-4 receptor subunit alpha

Gene

Il4r

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.

GO - Molecular functioni

GO - Biological processi

  • defense response to protozoan Source: MGI
  • immunoglobulin mediated immune response Source: MGI
  • negative regulation of T-helper 1 cell differentiation Source: MGI
  • ovulation Source: Ensembl
  • positive regulation of chemokine secretion Source: BHF-UCL
  • positive regulation of immunoglobulin production Source: MGI
  • positive regulation of macrophage activation Source: BHF-UCL
  • positive regulation of mast cell degranulation Source: MGI
  • positive regulation of myoblast fusion Source: MGI
  • positive regulation of T-helper 2 cell differentiation Source: MGI
  • production of molecular mediator involved in inflammatory response Source: InterPro
  • regulation of cell proliferation Source: Ensembl
  • response to estrogen Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:105367. Il4ra.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 233ExtracellularSequence analysisAdd BLAST208
Transmembranei234 – 257HelicalSequence analysisAdd BLAST24
Topological domaini258 – 810CytoplasmicSequence analysisAdd BLAST553

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 251 PublicationAdd BLAST25
ChainiPRO_000001088926 – 810Interleukin-4 receptor subunit alphaAdd BLAST785
ChainiPRO_000001089026 – ?Soluble interleukin-4 receptor subunit alpha

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 44By similarity
Glycosylationi72N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi75 ↔ 87By similarity
Glycosylationi129N-linked (GlcNAc...)Sequence analysis1
Glycosylationi135N-linked (GlcNAc...)Sequence analysis1
Glycosylationi163N-linked (GlcNAc...)1
Modified residuei165PhosphoserineCombined sources1
Modified residuei500PhosphotyrosineBy similarity1
Modified residuei575Phosphotyrosine1 Publication1
Modified residuei603Phosphotyrosine1 Publication1
Modified residuei631Phosphotyrosine1 Publication1

Post-translational modificationi

On IL4 binding, phosphorylated on C-terminal tyrosine residues.1 Publication
Soluble IL4R can also be produced by proteolytic cleavage at the cell surface (shedding).1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP16382.
PaxDbiP16382.
PRIDEiP16382.

PTM databases

iPTMnetiP16382.
PhosphoSitePlusiP16382.

Expressioni

Tissue specificityi

Expressed in both Th1 and Th2 cells.

Gene expression databases

BgeeiENSMUSG00000030748.
CleanExiMM_IL4RA.
ExpressionAtlasiP16382. baseline and differential.
GenevisibleiP16382. MM.

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. 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 similarity2 Publications

Protein-protein interaction databases

BioGridi200638. 3 interactors.
DIPiDIP-1168N.
STRINGi10090.ENSMUSP00000033004.

Structurei

3D structure databases

ProteinModelPortaliP16382.
SMRiP16382.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 224Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni441 – 557Required for IRS1 activation and IL4-induced cell growthBy similarityAdd BLAST117
Regioni557 – 653Required for IL4-induced gene expressionBy similarityAdd BLAST97

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi213 – 217WSXWS motif5
Motifi263 – 271Box 1 motif9
Motifi707 – 712ITIM motif6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi376 – 381Poly-Glu6
Compositional biasi527 – 530Poly-Glu4

Domaini

The extracellular domain represents the IL4 binding protein (IL4BP).By similarity
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

eggNOGiENOG410IGBQ. Eukaryota.
ENOG41124QC. LUCA.
GeneTreeiENSGT00510000049182.
HOGENOMiHOG000090263.
HOVERGENiHBG052116.
InParanoidiP16382.
KOiK05071.
OMAiSPCCGCC.
OrthoDBiEOG091G010H.
PhylomeDBiP16382.
TreeFamiTF337996.

Family and domain databases

CDDicd00063. FN3. 1 hit.
Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
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]
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. AlignAdd to basket

Isoform 1 (identifier: P16382-1) [UniParc]FASTAAdd to basket
Also known as: Membrane

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

        10         20         30         40         50
MGRLCTKFLT SVGCLILLLV TGSGSIKVLG EPTCFSDYIR TSTCEWFLDS
60 70 80 90 100
AVDCSSQLCL HYRLMFFEFS ENLTCIPRNS ASTVCVCHME MNRPVQSDRY
110 120 130 140 150
QMELWAEHRQ LWQGSFSPSG NVKPLAPDNL TLHTNVSDEW LLTWNNLYPS
160 170 180 190 200
NNLLYKDLIS MVNISREDNP AEFIVYNVTY KEPRLSFPIN ILMSGVYYTA
210 220 230 240 250
RVRVRSQILT GTWSEWSPSI TWYNHFQLPL IQRLPLGVTI SCLCIPLFCL
260 270 280 290 300
FCYFSITKIK KIWWDQIPTP ARSPLVAIII QDAQVPLWDK QTRSQESTKY
310 320 330 340 350
PHWKTCLDKL LPCLLKHRVK KKTDFPKAAP TKSLQSPGKA GWCPMEVSRT
360 370 380 390 400
VLWPENVSVS VVRCMELFEA PVQNVEEEED EIVKEDLSMS PENSGGCGFQ
410 420 430 440 450
ESQADIMARL TENLFSDLLE AENGGLGQSA LAESCSPLPS GSGQASVSWA
460 470 480 490 500
CLPMGPSEEA TCQVTEQPSH PGPLSGSPAQ SAPTLACTQV PLVLADNPAY
510 520 530 540 550
RSFSDCCSPA PNPGELAPEQ QQADHLEEEE PPSPADPHSS GPPMQPVESW
560 570 580 590 600
EQILHMSVLQ HGAAAGSTPA PAGGYQEFVQ AVKQGAAQDP GVPGVRPSGD
610 620 630 640 650
PGYKAFSSLL SSNGIRGDTA AAGTDDGHGG YKPFQNPVPN QSPSSVPLFT
660 670 680 690 700
FGLDTELSPS PLNSDPPKSP PECLGLELGL KGGDWVKAPP PADQVPKPFG
710 720 730 740 750
DDLGFGIVYS SLTCHLCGHL KQHHSQEEGG QSPIVASPGC GCCYDDRSPS
760 770 780 790 800
LGSLSGALES CPEGIPPEAN LMSAPKTPSN LSGEGKGPGH SPVPSQTTEV
810
PVGALGIAVS
Note: Binds IL-4.
Length:810
Mass (Da):87,627
Last modified:August 1, 1990 - v1
Checksum:i536B9E01E938FF6D
GO
Isoform 2 (identifier: P16382-2) [UniParc]FASTAAdd to basket
Also known as: Secreted

The sequence of this isoform differs from the canonical sequence as follows:
     225-230: HFQLPL → PSNENL
     231-810: Missing.

Note: Binds IL-4.
Show »
Length:230
Mass (Da):26,456
Checksum:i0E6752D46475D97C
GO
Isoform 3 (identifier: P16382-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     258-810: Missing.

Note: Lacks the cytoplasmic domain. Binds IL4.
Show »
Length:257
Mass (Da):29,584
Checksum:i7E6E02C8A03045D5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti436S → C in BAC28718 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti59C → R in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti74T → I in strain: BALB/c, AKR/J and SJL/J; reduced IL4-neutralizing capacity of soluble form. 1 Publication1
Natural varianti193M → T in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti334L → P in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti374N → S in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti382I → M in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti472G → D in strain: BALB/c, AKR/J and SJL/J. 1
Natural varianti626D → G in strain: BALB/c, AKR/J and SJL/J. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001675225 – 230HFQLPL → PSNENL in isoform 2. 1 Publication6
Alternative sequenceiVSP_001676231 – 810Missing in isoform 2. 1 PublicationAdd BLAST580
Alternative sequenceiVSP_001677258 – 810Missing in isoform 3. 1 PublicationAdd BLAST553

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27959 mRNA. Translation: AAA39299.1.
M27960 mRNA. Translation: AAA39300.1.
M29854 mRNA. Translation: AAA39297.1.
M64879
, M64870, M64871, M64872, M64873, M64874, M64876, M64877, M64878 Genomic DNA. Translation: AAB59727.1.
AF000304 mRNA. Translation: AAB87750.1.
AK034466 mRNA. Translation: BAC28718.1.
AK088086 mRNA. Translation: BAC40137.1.
CCDSiCCDS40121.1. [P16382-1]
PIRiA33380.
RefSeqiNP_001008700.1. NM_001008700.3. [P16382-1]
UniGeneiMm.233802.

Genome annotation databases

EnsembliENSMUST00000033004; ENSMUSP00000033004; ENSMUSG00000030748. [P16382-1]
ENSMUST00000206846; ENSMUSP00000145824; ENSMUSG00000030748. [P16382-2]
GeneIDi16190.
KEGGimmu:16190.
UCSCiuc009jqc.1. mouse. [P16382-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27959 mRNA. Translation: AAA39299.1.
M27960 mRNA. Translation: AAA39300.1.
M29854 mRNA. Translation: AAA39297.1.
M64879
, M64870, M64871, M64872, M64873, M64874, M64876, M64877, M64878 Genomic DNA. Translation: AAB59727.1.
AF000304 mRNA. Translation: AAB87750.1.
AK034466 mRNA. Translation: BAC28718.1.
AK088086 mRNA. Translation: BAC40137.1.
CCDSiCCDS40121.1. [P16382-1]
PIRiA33380.
RefSeqiNP_001008700.1. NM_001008700.3. [P16382-1]
UniGeneiMm.233802.

3D structure databases

ProteinModelPortaliP16382.
SMRiP16382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200638. 3 interactors.
DIPiDIP-1168N.
STRINGi10090.ENSMUSP00000033004.

PTM databases

iPTMnetiP16382.
PhosphoSitePlusiP16382.

Proteomic databases

EPDiP16382.
PaxDbiP16382.
PRIDEiP16382.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033004; ENSMUSP00000033004; ENSMUSG00000030748. [P16382-1]
ENSMUST00000206846; ENSMUSP00000145824; ENSMUSG00000030748. [P16382-2]
GeneIDi16190.
KEGGimmu:16190.
UCSCiuc009jqc.1. mouse. [P16382-1]

Organism-specific databases

CTDi16190.
MGIiMGI:105367. Il4ra.

Phylogenomic databases

eggNOGiENOG410IGBQ. Eukaryota.
ENOG41124QC. LUCA.
GeneTreeiENSGT00510000049182.
HOGENOMiHOG000090263.
HOVERGENiHBG052116.
InParanoidiP16382.
KOiK05071.
OMAiSPCCGCC.
OrthoDBiEOG091G010H.
PhylomeDBiP16382.
TreeFamiTF337996.

Miscellaneous databases

PROiP16382.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030748.
CleanExiMM_IL4RA.
ExpressionAtlasiP16382. baseline and differential.
GenevisibleiP16382. MM.

Family and domain databases

CDDicd00063. FN3. 1 hit.
Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
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]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01355. HEMATOPO_REC_S_F1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIL4RA_MOUSE
AccessioniPrimary (citable) accession number: P16382
Secondary accession number(s): O54690, Q60583, Q8CBW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 30, 2016
This is version 172 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The sequences from strains C3H, CBA, DBA/2 and FVB/N are all identical to the one displayed.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.