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Protein

Interleukin-4 receptor subunit alpha

Gene

Il4r

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

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
  • 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

Keywordsi

Molecular functionReceptor
Biological processImmunity

Enzyme and pathway databases

ReactomeiR-MMU-6785807 Interleukin-4 and 13 signaling

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:105367 Il4ra

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Disulfide bondi75 ↔ 87By similarity
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi163N-linked (GlcNAc...) asparagine1
Modified residuei165PhosphoserineCombined sources1
Modified residuei500PhosphotyrosineBy similarity1
Modified residuei575PhosphotyrosineBy similarity1
Modified residuei603PhosphotyrosineBy similarity1
Modified residuei631PhosphotyrosineBy similarity1

Post-translational modificationi

On IL4 binding, phosphorylated on C-terminal tyrosine residues.By similarity
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 the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP. Interacts with JAK3 (By similarity). Interacts with PIK3C3 (PubMed:8390454). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5 (PubMed:12242343). Interacts with SOCS5; inhibits IL4 signaling (PubMed:12242343). Interacts with CLM1 (PubMed:26124135).By similarity3 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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR003531 Hempt_rcpt_S_F1_CS
IPR013783 Ig-like_fold
IPR015319 IL-4_rcpt-alpha_N
PfamiView protein in Pfam
PF09238 IL4Ra_N, 1 hit
SUPFAMiSSF49265 SSF49265, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01355 HEMATOPO_REC_S_F1, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiIL4RA_MOUSE
AccessioniPrimary (citable) accession number: P16382
Secondary accession number(s): O54690, Q60583, Q8CBW5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: March 28, 2018
This is version 179 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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