IL4RA_RAT
ID IL4RA_RAT Reviewed; 801 AA.
AC Q63257; Q9R1W8; Q9WTM8;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Interleukin-4 receptor subunit alpha;
DE Short=IL-4 receptor subunit alpha;
DE Short=IL-4R subunit alpha;
DE Short=IL-4R-alpha;
DE Short=IL-4RA;
DE AltName: CD_antigen=CD124;
DE Flags: Precursor;
GN Name=Il4r; Synonyms=Il4ra;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Wistar; TISSUE=Spleen;
RX PubMed=7640343; DOI=10.1006/cyto.1995.0027;
RA Richter G., Hein G., Blankenstein T., Diamantstein T.;
RT "The rat interleukin 4 receptor: coevolution of ligand and receptor.";
RL Cytokine 7:237-241(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
RX PubMed=10525162; DOI=10.1016/s0167-4889(99)00117-2;
RA Chen G., Nagasawa R., Imasawa T., Eto Y., Kikuchi K., Maruyama N.;
RT "Identification of soluble interleukin-4 receptor in rat glomerular
RT epithelial cells.";
RL Biochim. Biophys. Acta 1452:79-88(1999).
CC -!- FUNCTION: Receptor for both interleukin 4 and interleukin 13. Couples
CC to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in
CC promoting Th2 differentiation. The IL4/IL13 responses are involved in
CC regulating IgE production and, chemokine and mucus production at sites
CC of allergic inflammation. In certain cell types, can signal through
CC activation of insulin receptor substrates, IRS1/IRS2 (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: Isoform 2 (soluble form) inhibits IL4-induced spleen cell
CC proliferation.
CC -!- SUBUNIT: The functional IL4 receptor is formed by initial binding of
CC IL4 to IL4R. Subsequent recruitment to the complex of the common gamma
CC chain, in immune cells, creates a type I receptor and, in non-immune
CC cells, of IL13RA1 forms a type II receptor. IL4R can also interact with
CC the IL13/IL13RA1 complex to form a similar type II receptor. Interacts
CC with PIK3C3. Interacts with the SH2-containing phosphatases,
CC PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP. Interacts with JAK1 through
CC a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5;
CC inhibits IL4 signaling. Interacts with JAK3. Interacts with CLM1.
CC {ECO:0000250|UniProtKB:P16382, ECO:0000250|UniProtKB:P24394}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Membrane-bound form, mIL4R;
CC IsoId=Q63257-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble form, sIL4R;
CC IsoId=Q63257-2; Sequence=VSP_011118, VSP_011119;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in kidney, spleen, lung and
CC liver.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC -!- PTM: On IL4 binding, phosphorylated on C-terminal tyrosine residues.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 4
CC subfamily. {ECO:0000305}.
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DR EMBL; X69903; CAA49528.1; -; mRNA.
DR EMBL; AB015746; BAA78337.1; -; mRNA.
DR EMBL; AB015747; BAA78338.1; -; mRNA.
DR PIR; S31575; S31575.
DR RefSeq; NP_596871.2; NM_133380.2. [Q63257-1]
DR RefSeq; XP_006230277.1; XM_006230215.3. [Q63257-1]
DR RefSeq; XP_006230278.1; XM_006230216.2. [Q63257-1]
DR RefSeq; XP_008758085.1; XM_008759863.2. [Q63257-1]
DR RefSeq; XP_008758086.1; XM_008759864.2. [Q63257-1]
DR RefSeq; XP_017444292.1; XM_017588803.1. [Q63257-1]
DR RefSeq; XP_017444293.1; XM_017588804.1. [Q63257-1]
DR AlphaFoldDB; Q63257; -.
DR SMR; Q63257; -.
DR STRING; 10116.ENSRNOP00000020994; -.
DR GlyGen; Q63257; 5 sites.
DR iPTMnet; Q63257; -.
DR PhosphoSitePlus; Q63257; -.
DR jPOST; Q63257; -.
DR PaxDb; Q63257; -.
DR PRIDE; Q63257; -.
DR Ensembl; ENSRNOT00000020994; ENSRNOP00000020994; ENSRNOG00000015441. [Q63257-1]
DR GeneID; 25084; -.
DR KEGG; rno:25084; -.
DR UCSC; RGD:2899; rat. [Q63257-1]
DR CTD; 3566; -.
DR RGD; 2899; Il4r.
DR eggNOG; ENOG502S3Y8; Eukaryota.
DR GeneTree; ENSGT00510000049182; -.
DR HOGENOM; CLU_020561_0_0_1; -.
DR InParanoid; Q63257; -.
DR OMA; GYKPFQN; -.
DR OrthoDB; 476828at2759; -.
DR PhylomeDB; Q63257; -.
DR TreeFam; TF337996; -.
DR Reactome; R-RNO-6785807; Interleukin-4 and Interleukin-13 signaling.
DR PRO; PR:Q63257; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000015441; Expressed in ileum and 18 other tissues.
DR Genevisible; Q63257; RN.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; TAS:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
DR GO; GO:0006955; P:immune response; TAS:RGD.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; TAS:RGD.
DR GO; GO:0045626; P:negative regulation of T-helper 1 cell differentiation; ISO:RGD.
DR GO; GO:0030728; P:ovulation; IEP:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISO:RGD.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:RGD.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISO:RGD.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISO:RGD.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISO:RGD.
DR GO; GO:0002532; P:production of molecular mediator involved in inflammatory response; IEA:InterPro.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:1990834; P:response to odorant; IEP:RGD.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR003531; Hempt_rcpt_S_F1_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015319; IL-4_rcpt-alpha_N.
DR Pfam; PF09238; IL4Ra_N; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01355; HEMATOPO_REC_S_F1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..801
FT /note="Interleukin-4 receptor subunit alpha"
FT /id="PRO_0000010892"
FT TOPO_DOM 26..232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..801
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 125..223
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 424..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..549
FT /note="Required for IRS1 activation and IL4-induced cell
FT growth"
FT /evidence="ECO:0000250"
FT REGION 493..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 549..644
FT /note="Required for IL4-induced gene expression"
FT /evidence="ECO:0000250"
FT REGION 767..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 212..216
FT /note="WSXWS motif"
FT MOTIF 262..270
FT /note="Box 1 motif"
FT MOTIF 698..703
FT /note="ITIM motif"
FT COMPBIAS 425..465
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 782..801
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16382"
FT MOD_RES 492
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P24394"
FT MOD_RES 566
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P24394"
FT MOD_RES 594
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P24394"
FT MOD_RES 622
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P24394"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..44
FT /evidence="ECO:0000250"
FT DISULFID 74..86
FT /evidence="ECO:0000250"
FT VAR_SEQ 224..229
FT /note="HFQLPL -> PNNVNL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10525162"
FT /id="VSP_011118"
FT VAR_SEQ 230..801
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10525162"
FT /id="VSP_011119"
FT CONFLICT 3
FT /note="W -> R (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="A -> G (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="S -> L (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
FT CONFLICT 580..582
FT /note="DAG -> ARW (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
FT CONFLICT 728
FT /note="S -> C (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
FT CONFLICT 776..777
FT /note="GK -> Q (in Ref. 1; CAA49528)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 801 AA; 86719 MW; 835E98D5E800EC76 CRC64;
MGWLCTKFLS SVSCLILLWV TGSGGIKVLG DPTCFSDYIR TSTCEWQLDS TVDCSSQLLL
DYRLLFEFSE NLTCTPKNSA DTVCVCQMAI EEPIQADTYW LELWSERGQL WQGSFKPSDN
VKPPAPDNLT LHTNVSNALL LMWSNPYPSN NFLHKGLICM VNISREDNPA EFKVYNVTYT
EPKLSFPVNT LTSGVRYRAR VRVLSQSFPG IWSEWSPSIT WYNHFQLPLL QRLPLGVSIS
CICILLFCLT CYFSIIKIKK IWWDQIPTPA RSPLAAIIIQ DTKVSLWEKQ TRSQESTKSR
HWKTCLTKLL PCLLEHRVKK ERESPKAAKT KPLQSPEKAG WYPAEVSRTV LWPENVHVSV
VRCMELFEAP VQNVEEEEDE MVKGDLSMSP ENSGGGFQES QADIMARLTE NLFSDLLGAE
NGGVGQSSMA ESSSLLPSES GQASTSWACF PTGPSETTCQ VTGQQPPHPD PERATGTACT
QVPLVISDNP AYRSFSDFSS PAPNPGELAS EQKQAGHLEE GDLLSPVDPH SSGPPMQQAE
SWEQILHMSV LQHGTAGSTP APTSGYQEFV QAVKQGASQD AGVPGVGPSG DTGYKAFSSL
LSSSGVCTDT AAAGTDSGCG GYKPFQNPVP NQSPNSMPLF TFGLDMELPP SPLNSAPPNS
TPECLGLELG LKGGTWLKAP PPSEQVPKPF GDDLGLGIVY SSLTCHLCGH LKQHHSQEED
GQIHVVASPG CGCCYDEKSP SLGNLSGTLE SCPGEMSQEA NLTLAPRTPS NLSGVGKGPG
HSPVPSQTTE VPVGTLGVTV S
