ID   IL3RA_MOUSE             Reviewed;         396 AA.
AC   P26952; B9VI80;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Interleukin-3 receptor subunit alpha;
DE            Short=IL-3 receptor subunit alpha;
DE            Short=IL-3R subunit alpha;
DE            Short=IL-3R-alpha;
DE            Short=IL-3RA;
DE   AltName: Full=Interleukin-3 receptor class II alpha chain;
DE   AltName: CD_antigen=CD123;
DE   Flags: Precursor;
GN   Name=Il3ra; Synonyms=Sut-1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=B6.S;
RX   PubMed=1582416; DOI=10.1002/j.1460-2075.1992.tb05239.x;
RA   Hara T., Miyajima A.;
RT   "Two distinct functional high affinity receptors for mouse interleukin-3
RT   (IL-3).";
RL   EMBO J. 11:1875-1884(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND SUBCELLULAR LOCATION.
RC   STRAIN=A/J, and C57BL/6J;
RX   PubMed=7889941; DOI=10.1002/j.1460-2075.1995.tb07075.x;
RA   Ichihara M., Hara T., Takagi M., Cho L.C., Gorman D.M., Miyajima A.;
RT   "Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a
RT   branch point deletion in the IL-3 receptor alpha subunit gene.";
RL   EMBO J. 14:939-950(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX   PubMed=19109256; DOI=10.1074/jbc.m808197200;
RA   Chen J., Olsen J., Ford S., Mirza S., Walker A., Murphy J.M., Young I.G.;
RT   "A new isoform of IL-3 receptor alpha with novel differentiation activity
RT   and high affinity binding mode.";
RL   J. Biol. Chem. 284:5763-5773(2009).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH IL3RB.
RX   PubMed=10477686;
RA   Orban P.C., Levings M.K., Schrader J.W.;
RT   "Heterodimerization of the alpha and beta chains of the interleukin-3 (IL-
RT   3) receptor is necessary and sufficient for IL-3-induced mitogenesis.";
RL   Blood 94:1614-1622(1999).
RN   [5]
RP   FUNCTION IN STAT5 ACTIVATION.
RX   PubMed=10376805; DOI=10.1016/s0898-6568(98)00049-7;
RA   Jaster R., Tschirch E., Bittorf T., Brock J.;
RT   "Role of STAT5 in interferon-alpha signal transduction in Ba/F3 cells.";
RL   Cell. Signal. 11:331-335(1999).
RN   [6]
RP   UBIQUITINATION AT LYS-357, MUTAGENESIS OF LYS-357, AND FUNCTION.
RX   PubMed=31990690; DOI=10.1172/jci.insight.133652;
RA   Tong Y., Lear T.B., Evankovich J., Chen Y., Londino J.D., Myerburg M.M.,
RA   Zhang Y., Popescu I.D., McDyer J.F., McVerry B.J., Lockwood K.C.,
RA   Jurczak M.J., Liu Y., Chen B.B.;
RT   "The RNFT2/IL-3Ralpha axis regulates IL-3 signaling and innate immunity.";
RL   JCI Insight 5:0-0(2020).
CC   -!- FUNCTION: Cell surface receptor for IL3 expressed on hematopoietic
CC       progenitor cells, monocytes and B-lymphocytes that controls the
CC       production and differentiation of hematopoietic progenitor cells into
CC       lineage-restricted cells (By similarity). Ligand stimulation rapidly
CC       induces hetrodimerization with IL3RB, phosphorylation and enzyme
CC       activity of effector proteins such as JAK2 and PI3K that play a role in
CC       signaling cell proliferation and differentiation (PubMed:10477686,
CC       PubMed:31990690). Activation of JAK2 leads to STAT5-mediated
CC       transcriptional program (PubMed:10376805).
CC       {ECO:0000250|UniProtKB:P26951, ECO:0000269|PubMed:10376805,
CC       ECO:0000269|PubMed:10477686, ECO:0000269|PubMed:31990690}.
CC   -!- SUBUNIT: Interacts with IL3. Heterodimer of an alpha and a beta subunit
CC       (PubMed:10477686). The beta subunit is common to the IL3, IL5 and GM-
CC       CSF receptors. {ECO:0000250|UniProtKB:P26951,
CC       ECO:0000269|PubMed:10477686}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC       membrane protein. Note=Expressed on the cell surface.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Endomembrane system; Single-pass
CC       type I membrane protein. Note=Mostly distributed inside the cells,
CC       except in the nuclei and is not transported to the cell surface.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=B, SP1;
CC         IsoId=P26952-1; Sequence=Displayed;
CC       Name=2; Synonyms=SP2;
CC         IsoId=P26952-3; Sequence=VSP_040623;
CC       Name=3; Synonyms=A;
CC         IsoId=P26952-2; Sequence=VSP_011265;
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   -!- PTM: Ubiquitinated at Lys-357 by RNFT2 in response to IL3.
CC       Ubiquitination leads ligand-induced degradation by the proteasome.
CC       {ECO:0000269|PubMed:31990690}.
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 5
CC       subfamily. {ECO:0000305}.
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DR   EMBL; X64534; CAA45833.1; -; mRNA.
DR   EMBL; FJ550346; ACM24115.1; -; mRNA.
DR   CCDS; CCDS26827.1; -. [P26952-1]
DR   PIR; S22909; S22909.
DR   RefSeq; NP_032395.1; NM_008369.1. [P26952-1]
DR   AlphaFoldDB; P26952; -.
DR   SMR; P26952; -.
DR   BioGRID; 200636; 3.
DR   DIP; DIP-59621N; -.
DR   IntAct; P26952; 1.
DR   STRING; 10090.ENSMUSP00000153358; -.
DR   GlyCosmos; P26952; 5 sites, No reported glycans.
DR   GlyGen; P26952; 5 sites.
DR   PhosphoSitePlus; P26952; -.
DR   SwissPalm; P26952; -.
DR   EPD; P26952; -.
DR   MaxQB; P26952; -.
DR   PaxDb; 10090-ENSMUSP00000088079; -.
DR   ProteomicsDB; 301647; -. [P26952-1]
DR   ProteomicsDB; 301648; -. [P26952-3]
DR   ProteomicsDB; 301649; -. [P26952-2]
DR   DNASU; 16188; -.
DR   Ensembl; ENSMUST00000090591.4; ENSMUSP00000088079.3; ENSMUSG00000068758.9. [P26952-1]
DR   Ensembl; ENSMUST00000224163.2; ENSMUSP00000153358.2; ENSMUSG00000068758.9. [P26952-1]
DR   Ensembl; ENSMUST00000224877.2; ENSMUSP00000153086.2; ENSMUSG00000068758.9. [P26952-3]
DR   GeneID; 16188; -.
DR   KEGG; mmu:16188; -.
DR   UCSC; uc007sgm.1; mouse. [P26952-1]
DR   UCSC; uc011zgb.1; mouse. [P26952-3]
DR   AGR; MGI:96553; -.
DR   CTD; 3563; -.
DR   MGI; MGI:96553; Il3ra.
DR   VEuPathDB; HostDB:ENSMUSG00000068758; -.
DR   eggNOG; ENOG502RZVR; Eukaryota.
DR   GeneTree; ENSGT00940000171119; -.
DR   HOGENOM; CLU_039627_1_0_1; -.
DR   InParanoid; P26952; -.
DR   OMA; TATCNKS; -.
DR   OrthoDB; 5353959at2759; -.
DR   PhylomeDB; P26952; -.
DR   TreeFam; TF331549; -.
DR   BioGRID-ORCS; 16188; 5 hits in 80 CRISPR screens.
DR   ChiTaRS; Slc13a4; mouse.
DR   PRO; PR:P26952; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; P26952; Protein.
DR   Bgee; ENSMUSG00000068758; Expressed in granulocyte and 89 other cell types or tissues.
DR   ExpressionAtlas; P26952; baseline and differential.
DR   GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004912; F:interleukin-3 receptor activity; ISO:MGI.
DR   GO; GO:0038156; P:interleukin-3-mediated signaling pathway; IDA:MGI.
DR   Gene3D; 2.60.40.3850; -; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003532; Short_hematopoietin_rcpt_2_CS.
DR   InterPro; IPR015321; TypeI_recpt_CBD.
DR   Pfam; PF09240; IL6Ra-bind; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 1.
DR   PROSITE; PS01356; HEMATOPO_REC_S_F2; 1.
DR   Genevisible; P26952; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW   Isopeptide bond; Membrane; Receptor; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..396
FT                   /note="Interleukin-3 receptor subunit alpha"
FT                   /id="PRO_0000010884"
FT   TOPO_DOM        17..331
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        332..355
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        356..396
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOTIF           312..316
FT                   /note="WSXWS motif"
FT   MOTIF           363..371
FT                   /note="Box 1 motif"
FT   CARBOHYD        91
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        213
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        272
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        283
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        62..79
FT                   /evidence="ECO:0000250|UniProtKB:P26951"
FT   DISULFID        87..223
FT                   /evidence="ECO:0000250|UniProtKB:P26951"
FT   DISULFID        125..134
FT                   /evidence="ECO:0000250|UniProtKB:P26951"
FT   DISULFID        165..187
FT                   /evidence="ECO:0000250|UniProtKB:P26951"
FT   DISULFID        245..323
FT                   /evidence="ECO:0000250|UniProtKB:P26951"
FT   CROSSLNK        357
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:31990690"
FT   VAR_SEQ         20..112
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:19109256"
FT                   /id="VSP_040623"
FT   VAR_SEQ         274..283
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:7889941"
FT                   /id="VSP_011265"
FT   MUTAGEN         357
FT                   /note="K->R: Resistant to degradation."
FT                   /evidence="ECO:0000269|PubMed:31990690"
FT   CONFLICT        113
FT                   /note="D -> G (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   396 AA;  43195 MW;  F1A5BF11743AB8A3 CRC64;
     MAANLWLILG LLASHSSDLA AVREAPPTAV TTPIQNLHID PAHYTLSWDP APGADITTGA
     FCRKGRDIFV WADPGLARCS FQSLSLCHVT NFTVFLGKDR AVAGSIQFPP DDDGDHEAAA
     QDLRCWVHEG QLSCQWERGP KATGDVHYRM FWRDVRLGPA HNRECPHYHS LDVNTAGPAP
     HGGHEGCTLD LDTVLGSTPN SPDLVPQVTI TVNGSGRAGP VPCMDNTVDL QRAEVLAPPT
     LTVECNGSEA HARWVARNRF HHGLLGYTLQ VNQSSRSEPQ EYNVSIPHFW VPNAGAISFR
     VKSRSEVYPR KLSSWSEAWG LVCPPEVMPV KTALVTSVAT VLGAGLVAAG LLLWWRKSLL
     YRLCPPIPRL RLPLAGEMVV WEPALEDCEV TPVTDA
//