Full text data of IL5RA
IL5RA
(IL5R)
[Confidence: high (a blood group or CD marker)]
Interleukin-5 receptor subunit alpha; IL-5 receptor subunit alpha; IL-5R subunit alpha; IL-5R-alpha; IL-5RA (CDw125; CD125; Flags: Precursor)
Interleukin-5 receptor subunit alpha; IL-5 receptor subunit alpha; IL-5R subunit alpha; IL-5R-alpha; IL-5RA (CDw125; CD125; Flags: Precursor)
UniProt
Q01344
ID IL5RA_HUMAN Reviewed; 420 AA.
AC Q01344; B3IU77; B4E2G0; Q14633; Q15469; Q6ISX9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Interleukin-5 receptor subunit alpha;
DE Short=IL-5 receptor subunit alpha;
DE Short=IL-5R subunit alpha;
DE Short=IL-5R-alpha;
DE Short=IL-5RA;
DE AltName: Full=CDw125;
DE AltName: CD_antigen=CD125;
DE Flags: Precursor;
GN Name=IL5RA; Synonyms=IL5R;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1833065; DOI=10.1016/0092-8674(91)90040-6;
RA Tavernier J., Devos R., Cornelis S., Tuypens T., van der Heyden J.,
RA Fiers W., Plaetinck G.;
RT "A human high affinity interleukin-5 receptor (IL5R) is composed of an
RT IL5-specific alpha chain and a beta chain shared with the receptor for
RT GM-CSF.";
RL Cell 66:1175-1184(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND VARIANT VAL-129.
RC TISSUE=Peripheral blood;
RX PubMed=1732409; DOI=10.1084/jem.175.2.341;
RA Murata Y., Takaki S., Migita M., Kikuchi Y., Tominaga A., Takatsu K.;
RT "Molecular cloning and expression of the human interleukin 5
RT receptor.";
RL J. Exp. Med. 175:341-351(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=1495999; DOI=10.1073/pnas.89.15.7041;
RA Tavernier J., Tuypens T., Plaetinck G., Verhee A., Fiers W., Devos R.;
RT "Molecular basis of the membrane-anchored and two soluble isoforms of
RT the human interleukin 5 receptor alpha subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7041-7045(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Ishihara K., Yamada M., Hirasawa N., Ohuchi K.;
RT "Isolation of the variants for human interleukin-5 receptor alpha
RT subunit.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-129 AND ALA-262.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 413-420 IN COMPLEX WITH
RP SDCBP.
RX PubMed=12842047; DOI=10.1016/S0969-2126(03)00125-4;
RA Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "Molecular roots of degenerate specificity in syntenin's PDZ2 domain:
RT reassessment of the PDZ recognition paradigm.";
RL Structure 11:845-853(2003).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 20-332 IN COMPLEX WITH IL5,
RP AND DISULFIDE BONDS.
RX PubMed=22153509; DOI=10.1016/j.str.2011.08.015;
RA Patino E., Kotzsch A., Saremba S., Nickel J., Schmitz W., Sebald W.,
RA Mueller T.D.;
RT "Structure analysis of the IL-5 ligand-receptor complex reveals a
RT wrench-like architecture for IL-5Ralpha.";
RL Structure 19:1864-1875(2011).
CC -!- FUNCTION: This is the receptor for interleukin-5. The alpha chain
CC binds to IL5.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The beta
CC subunit is common to the IL3, IL5 and GM-CSF receptors. Interacts
CC with SDCBP.
CC -!- INTERACTION:
CC P05113:IL5; NbExp=2; IntAct=EBI-1759442, EBI-2435811;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Membrane-bound;
CC IsoId=Q01344-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble-S1;
CC IsoId=Q01344-2; Sequence=VSP_001678, VSP_001679;
CC Name=3; Synonyms=Soluble-S2;
CC IsoId=Q01344-3; Sequence=VSP_001680, VSP_001681;
CC Name=4;
CC IsoId=Q01344-4; Sequence=VSP_046742;
CC Name=5;
CC IsoId=Q01344-5; Sequence=VSP_047762;
CC -!- TISSUE SPECIFICITY: Expressed on eosinophils and basophils.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-
CC surface receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 5
CC subfamily.
CC -!- SIMILARITY: Contains 2 fibronectin type-III domains.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il5ra/";
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DR EMBL; M75914; AAA36110.1; -; mRNA.
DR EMBL; X61176; CAA43483.1; -; mRNA.
DR EMBL; X62156; CAA44081.1; -; mRNA.
DR EMBL; M96651; AAA59151.1; -; mRNA.
DR EMBL; M96652; AAA59152.1; -; mRNA.
DR EMBL; AB288090; BAG49562.1; -; mRNA.
DR EMBL; AK304256; BAG65122.1; -; mRNA.
DR EMBL; AY642135; AAT45457.1; -; Genomic_DNA.
DR EMBL; AC022002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A40267; A40267.
DR RefSeq; NP_000555.2; NM_000564.4.
DR RefSeq; NP_001230028.1; NM_001243099.1.
DR RefSeq; NP_783851.1; NM_175724.2.
DR RefSeq; NP_783852.1; NM_175725.2.
DR RefSeq; NP_783853.1; NM_175726.3.
DR RefSeq; NP_783854.1; NM_175727.2.
DR RefSeq; NP_783855.1; NM_175728.2.
DR UniGene; Hs.68876; -.
DR PDB; 1OBX; X-ray; 1.35 A; B=413-420.
DR PDB; 1OBZ; X-ray; 1.69 A; P=413-420.
DR PDB; 3QT2; X-ray; 2.55 A; A/B=20-332.
DR PDB; 3VA2; X-ray; 2.70 A; C=21-335.
DR PDBsum; 1OBX; -.
DR PDBsum; 1OBZ; -.
DR PDBsum; 3QT2; -.
DR PDBsum; 3VA2; -.
DR ProteinModelPortal; Q01344; -.
DR SMR; Q01344; 27-333.
DR DIP; DIP-3510N; -.
DR IntAct; Q01344; 3.
DR STRING; 9606.ENSP00000256452; -.
DR GuidetoPHARMACOLOGY; 1706; -.
DR PhosphoSite; Q01344; -.
DR DMDM; 116242525; -.
DR PaxDb; Q01344; -.
DR PRIDE; Q01344; -.
DR Ensembl; ENST00000256452; ENSP00000256452; ENSG00000091181.
DR Ensembl; ENST00000311981; ENSP00000309196; ENSG00000091181.
DR Ensembl; ENST00000383846; ENSP00000373358; ENSG00000091181.
DR Ensembl; ENST00000430514; ENSP00000400400; ENSG00000091181.
DR Ensembl; ENST00000438560; ENSP00000390753; ENSG00000091181.
DR Ensembl; ENST00000445864; ENSP00000402598; ENSG00000091181.
DR Ensembl; ENST00000446632; ENSP00000412209; ENSG00000091181.
DR Ensembl; ENST00000456302; ENSP00000392059; ENSG00000091181.
DR GeneID; 3568; -.
DR KEGG; hsa:3568; -.
DR UCSC; uc010hbr.3; human.
DR CTD; 3568; -.
DR GeneCards; GC03M003111; -.
DR HGNC; HGNC:6017; IL5RA.
DR HPA; HPA013196; -.
DR MIM; 147851; gene.
DR neXtProt; NX_Q01344; -.
DR PharmGKB; PA29834; -.
DR eggNOG; NOG43089; -.
DR HOGENOM; HOG000070224; -.
DR HOVERGEN; HBG052117; -.
DR InParanoid; Q01344; -.
DR KO; K05067; -.
DR OMA; APEDTQY; -.
DR OrthoDB; EOG71P2B1; -.
DR PhylomeDB; Q01344; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q01344; -.
DR EvolutionaryTrace; Q01344; -.
DR GeneWiki; Interleukin_5_receptor_alpha_subunit; -.
DR GenomeRNAi; 3568; -.
DR NextBio; 13936; -.
DR PRO; PR:Q01344; -.
DR ArrayExpress; Q01344; -.
DR Bgee; Q01344; -.
DR CleanEx; HS_IL5RA; -.
DR Genevestigator; Q01344; -.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0016021; C:integral to membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004914; F:interleukin-5 receptor activity; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0032674; P:regulation of interleukin-5 production; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015321; IL-6_rcpt_alpha-bd.
DR InterPro; IPR003532; Short_hematopoietin_rcpt_2_CS.
DR Pfam; PF09240; IL6Ra-bind; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01356; HEMATOPO_REC_S_F2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Disulfide bond;
KW Glycoprotein; Membrane; Polymorphism; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 20
FT CHAIN 21 420 Interleukin-5 receptor subunit alpha.
FT /FTId=PRO_0000010893.
FT TOPO_DOM 21 342 Extracellular (Potential).
FT TRANSMEM 343 362 Helical; (Potential).
FT TOPO_DOM 363 420 Cytoplasmic (Potential).
FT DOMAIN 32 123 Fibronectin type-III 1.
FT DOMAIN 241 334 Fibronectin type-III 2.
FT MOTIF 322 326 WSXWS motif.
FT MOTIF 371 379 Box 1 motif.
FT CARBOHYD 35 35 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 131 131 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 216 216 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 244 244 N-linked (GlcNAc...) (Potential).
FT DISULFID 134 155
FT DISULFID 182 196
FT DISULFID 269 316
FT VAR_SEQ 123 331 Missing (in isoform 5).
FT /FTId=VSP_047762.
FT VAR_SEQ 333 335 NDE -> FSR (in isoform 2).
FT /FTId=VSP_001678.
FT VAR_SEQ 333 333 N -> K (in isoform 3).
FT /FTId=VSP_001680.
FT VAR_SEQ 334 420 Missing (in isoform 3).
FT /FTId=VSP_001681.
FT VAR_SEQ 336 420 Missing (in isoform 2).
FT /FTId=VSP_001679.
FT VAR_SEQ 365 420 CHLWIKLFPPIPAPKSNIKDLFVTTNYEKAGSSETEIEVIC
FT YIEKPGVETLEDSVF -> KLGPVRRKLKSSVI (in
FT isoform 4).
FT /FTId=VSP_046742.
FT VARIANT 129 129 I -> V (in dbSNP:rs2290610).
FT /FTId=VAR_020654.
FT VARIANT 262 262 V -> A (in dbSNP:rs17879690).
FT /FTId=VAR_020655.
FT CONFLICT 212 212 A -> S (in Ref. 1; AAA36110 and 2;
FT AAA59151/AAA59152).
FT STRAND 34 42
FT STRAND 45 51
FT STRAND 59 61
FT STRAND 64 73
FT STRAND 75 87
FT STRAND 94 103
FT STRAND 108 110
FT STRAND 114 118
FT STRAND 122 124
FT HELIX 125 127
FT STRAND 130 140
FT STRAND 144 146
FT STRAND 149 158
FT STRAND 168 175
FT STRAND 178 181
FT STRAND 185 187
FT STRAND 193 200
FT STRAND 209 218
FT STRAND 227 232
FT HELIX 233 236
FT STRAND 243 250
FT STRAND 253 259
FT STRAND 262 265
FT HELIX 267 269
FT STRAND 270 278
FT TURN 279 281
FT STRAND 284 297
FT STRAND 304 312
FT TURN 314 316
FT STRAND 329 331
SQ SEQUENCE 420 AA; 47685 MW; 4E0A5F2838B9C4FE CRC64;
MIIVAHVLLI LLGATEILQA DLLPDEKISL LPPVNFTIKV TGLAQVLLQW KPNPDQEQRN
VNLEYQVKIN APKEDDYETR ITESKCVTIL HKGFSASVRT ILQNDHSLLA SSWASAELHA
PPGSPGTSIV NLTCTTNTTE DNYSRLRSYQ VSLHCTWLVG TDAPEDTQYF LYYRYGSWTE
ECQEYSKDTL GRNIACWFPR TFILSKGRDW LAVLVNGSSK HSAIRPFDQL FALHAIDQIN
PPLNVTAEIE GTRLSIQWEK PVSAFPIHCF DYEVKIHNTR NGYLQIEKLM TNAFISIIDD
LSKYDVQVRA AVSSMCREAG LWSEWSQPIY VGNDEHKPLR EWFVIVIMAT ICFILLILSL
ICKICHLWIK LFPPIPAPKS NIKDLFVTTN YEKAGSSETE IEVICYIEKP GVETLEDSVF
//
ID IL5RA_HUMAN Reviewed; 420 AA.
AC Q01344; B3IU77; B4E2G0; Q14633; Q15469; Q6ISX9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Interleukin-5 receptor subunit alpha;
DE Short=IL-5 receptor subunit alpha;
DE Short=IL-5R subunit alpha;
DE Short=IL-5R-alpha;
DE Short=IL-5RA;
DE AltName: Full=CDw125;
DE AltName: CD_antigen=CD125;
DE Flags: Precursor;
GN Name=IL5RA; Synonyms=IL5R;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1833065; DOI=10.1016/0092-8674(91)90040-6;
RA Tavernier J., Devos R., Cornelis S., Tuypens T., van der Heyden J.,
RA Fiers W., Plaetinck G.;
RT "A human high affinity interleukin-5 receptor (IL5R) is composed of an
RT IL5-specific alpha chain and a beta chain shared with the receptor for
RT GM-CSF.";
RL Cell 66:1175-1184(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND VARIANT VAL-129.
RC TISSUE=Peripheral blood;
RX PubMed=1732409; DOI=10.1084/jem.175.2.341;
RA Murata Y., Takaki S., Migita M., Kikuchi Y., Tominaga A., Takatsu K.;
RT "Molecular cloning and expression of the human interleukin 5
RT receptor.";
RL J. Exp. Med. 175:341-351(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=1495999; DOI=10.1073/pnas.89.15.7041;
RA Tavernier J., Tuypens T., Plaetinck G., Verhee A., Fiers W., Devos R.;
RT "Molecular basis of the membrane-anchored and two soluble isoforms of
RT the human interleukin 5 receptor alpha subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7041-7045(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Ishihara K., Yamada M., Hirasawa N., Ohuchi K.;
RT "Isolation of the variants for human interleukin-5 receptor alpha
RT subunit.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-129 AND ALA-262.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 413-420 IN COMPLEX WITH
RP SDCBP.
RX PubMed=12842047; DOI=10.1016/S0969-2126(03)00125-4;
RA Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "Molecular roots of degenerate specificity in syntenin's PDZ2 domain:
RT reassessment of the PDZ recognition paradigm.";
RL Structure 11:845-853(2003).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 20-332 IN COMPLEX WITH IL5,
RP AND DISULFIDE BONDS.
RX PubMed=22153509; DOI=10.1016/j.str.2011.08.015;
RA Patino E., Kotzsch A., Saremba S., Nickel J., Schmitz W., Sebald W.,
RA Mueller T.D.;
RT "Structure analysis of the IL-5 ligand-receptor complex reveals a
RT wrench-like architecture for IL-5Ralpha.";
RL Structure 19:1864-1875(2011).
CC -!- FUNCTION: This is the receptor for interleukin-5. The alpha chain
CC binds to IL5.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The beta
CC subunit is common to the IL3, IL5 and GM-CSF receptors. Interacts
CC with SDCBP.
CC -!- INTERACTION:
CC P05113:IL5; NbExp=2; IntAct=EBI-1759442, EBI-2435811;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Membrane-bound;
CC IsoId=Q01344-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble-S1;
CC IsoId=Q01344-2; Sequence=VSP_001678, VSP_001679;
CC Name=3; Synonyms=Soluble-S2;
CC IsoId=Q01344-3; Sequence=VSP_001680, VSP_001681;
CC Name=4;
CC IsoId=Q01344-4; Sequence=VSP_046742;
CC Name=5;
CC IsoId=Q01344-5; Sequence=VSP_047762;
CC -!- TISSUE SPECIFICITY: Expressed on eosinophils and basophils.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-
CC surface receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 5
CC subfamily.
CC -!- SIMILARITY: Contains 2 fibronectin type-III domains.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il5ra/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M75914; AAA36110.1; -; mRNA.
DR EMBL; X61176; CAA43483.1; -; mRNA.
DR EMBL; X62156; CAA44081.1; -; mRNA.
DR EMBL; M96651; AAA59151.1; -; mRNA.
DR EMBL; M96652; AAA59152.1; -; mRNA.
DR EMBL; AB288090; BAG49562.1; -; mRNA.
DR EMBL; AK304256; BAG65122.1; -; mRNA.
DR EMBL; AY642135; AAT45457.1; -; Genomic_DNA.
DR EMBL; AC022002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A40267; A40267.
DR RefSeq; NP_000555.2; NM_000564.4.
DR RefSeq; NP_001230028.1; NM_001243099.1.
DR RefSeq; NP_783851.1; NM_175724.2.
DR RefSeq; NP_783852.1; NM_175725.2.
DR RefSeq; NP_783853.1; NM_175726.3.
DR RefSeq; NP_783854.1; NM_175727.2.
DR RefSeq; NP_783855.1; NM_175728.2.
DR UniGene; Hs.68876; -.
DR PDB; 1OBX; X-ray; 1.35 A; B=413-420.
DR PDB; 1OBZ; X-ray; 1.69 A; P=413-420.
DR PDB; 3QT2; X-ray; 2.55 A; A/B=20-332.
DR PDB; 3VA2; X-ray; 2.70 A; C=21-335.
DR PDBsum; 1OBX; -.
DR PDBsum; 1OBZ; -.
DR PDBsum; 3QT2; -.
DR PDBsum; 3VA2; -.
DR ProteinModelPortal; Q01344; -.
DR SMR; Q01344; 27-333.
DR DIP; DIP-3510N; -.
DR IntAct; Q01344; 3.
DR STRING; 9606.ENSP00000256452; -.
DR GuidetoPHARMACOLOGY; 1706; -.
DR PhosphoSite; Q01344; -.
DR DMDM; 116242525; -.
DR PaxDb; Q01344; -.
DR PRIDE; Q01344; -.
DR Ensembl; ENST00000256452; ENSP00000256452; ENSG00000091181.
DR Ensembl; ENST00000311981; ENSP00000309196; ENSG00000091181.
DR Ensembl; ENST00000383846; ENSP00000373358; ENSG00000091181.
DR Ensembl; ENST00000430514; ENSP00000400400; ENSG00000091181.
DR Ensembl; ENST00000438560; ENSP00000390753; ENSG00000091181.
DR Ensembl; ENST00000445864; ENSP00000402598; ENSG00000091181.
DR Ensembl; ENST00000446632; ENSP00000412209; ENSG00000091181.
DR Ensembl; ENST00000456302; ENSP00000392059; ENSG00000091181.
DR GeneID; 3568; -.
DR KEGG; hsa:3568; -.
DR UCSC; uc010hbr.3; human.
DR CTD; 3568; -.
DR GeneCards; GC03M003111; -.
DR HGNC; HGNC:6017; IL5RA.
DR HPA; HPA013196; -.
DR MIM; 147851; gene.
DR neXtProt; NX_Q01344; -.
DR PharmGKB; PA29834; -.
DR eggNOG; NOG43089; -.
DR HOGENOM; HOG000070224; -.
DR HOVERGEN; HBG052117; -.
DR InParanoid; Q01344; -.
DR KO; K05067; -.
DR OMA; APEDTQY; -.
DR OrthoDB; EOG71P2B1; -.
DR PhylomeDB; Q01344; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q01344; -.
DR EvolutionaryTrace; Q01344; -.
DR GeneWiki; Interleukin_5_receptor_alpha_subunit; -.
DR GenomeRNAi; 3568; -.
DR NextBio; 13936; -.
DR PRO; PR:Q01344; -.
DR ArrayExpress; Q01344; -.
DR Bgee; Q01344; -.
DR CleanEx; HS_IL5RA; -.
DR Genevestigator; Q01344; -.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0016021; C:integral to membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004914; F:interleukin-5 receptor activity; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0032674; P:regulation of interleukin-5 production; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015321; IL-6_rcpt_alpha-bd.
DR InterPro; IPR003532; Short_hematopoietin_rcpt_2_CS.
DR Pfam; PF09240; IL6Ra-bind; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01356; HEMATOPO_REC_S_F2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Disulfide bond;
KW Glycoprotein; Membrane; Polymorphism; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 20
FT CHAIN 21 420 Interleukin-5 receptor subunit alpha.
FT /FTId=PRO_0000010893.
FT TOPO_DOM 21 342 Extracellular (Potential).
FT TRANSMEM 343 362 Helical; (Potential).
FT TOPO_DOM 363 420 Cytoplasmic (Potential).
FT DOMAIN 32 123 Fibronectin type-III 1.
FT DOMAIN 241 334 Fibronectin type-III 2.
FT MOTIF 322 326 WSXWS motif.
FT MOTIF 371 379 Box 1 motif.
FT CARBOHYD 35 35 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 131 131 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 216 216 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 244 244 N-linked (GlcNAc...) (Potential).
FT DISULFID 134 155
FT DISULFID 182 196
FT DISULFID 269 316
FT VAR_SEQ 123 331 Missing (in isoform 5).
FT /FTId=VSP_047762.
FT VAR_SEQ 333 335 NDE -> FSR (in isoform 2).
FT /FTId=VSP_001678.
FT VAR_SEQ 333 333 N -> K (in isoform 3).
FT /FTId=VSP_001680.
FT VAR_SEQ 334 420 Missing (in isoform 3).
FT /FTId=VSP_001681.
FT VAR_SEQ 336 420 Missing (in isoform 2).
FT /FTId=VSP_001679.
FT VAR_SEQ 365 420 CHLWIKLFPPIPAPKSNIKDLFVTTNYEKAGSSETEIEVIC
FT YIEKPGVETLEDSVF -> KLGPVRRKLKSSVI (in
FT isoform 4).
FT /FTId=VSP_046742.
FT VARIANT 129 129 I -> V (in dbSNP:rs2290610).
FT /FTId=VAR_020654.
FT VARIANT 262 262 V -> A (in dbSNP:rs17879690).
FT /FTId=VAR_020655.
FT CONFLICT 212 212 A -> S (in Ref. 1; AAA36110 and 2;
FT AAA59151/AAA59152).
FT STRAND 34 42
FT STRAND 45 51
FT STRAND 59 61
FT STRAND 64 73
FT STRAND 75 87
FT STRAND 94 103
FT STRAND 108 110
FT STRAND 114 118
FT STRAND 122 124
FT HELIX 125 127
FT STRAND 130 140
FT STRAND 144 146
FT STRAND 149 158
FT STRAND 168 175
FT STRAND 178 181
FT STRAND 185 187
FT STRAND 193 200
FT STRAND 209 218
FT STRAND 227 232
FT HELIX 233 236
FT STRAND 243 250
FT STRAND 253 259
FT STRAND 262 265
FT HELIX 267 269
FT STRAND 270 278
FT TURN 279 281
FT STRAND 284 297
FT STRAND 304 312
FT TURN 314 316
FT STRAND 329 331
SQ SEQUENCE 420 AA; 47685 MW; 4E0A5F2838B9C4FE CRC64;
MIIVAHVLLI LLGATEILQA DLLPDEKISL LPPVNFTIKV TGLAQVLLQW KPNPDQEQRN
VNLEYQVKIN APKEDDYETR ITESKCVTIL HKGFSASVRT ILQNDHSLLA SSWASAELHA
PPGSPGTSIV NLTCTTNTTE DNYSRLRSYQ VSLHCTWLVG TDAPEDTQYF LYYRYGSWTE
ECQEYSKDTL GRNIACWFPR TFILSKGRDW LAVLVNGSSK HSAIRPFDQL FALHAIDQIN
PPLNVTAEIE GTRLSIQWEK PVSAFPIHCF DYEVKIHNTR NGYLQIEKLM TNAFISIIDD
LSKYDVQVRA AVSSMCREAG LWSEWSQPIY VGNDEHKPLR EWFVIVIMAT ICFILLILSL
ICKICHLWIK LFPPIPAPKS NIKDLFVTTN YEKAGSSETE IEVICYIEKP GVETLEDSVF
//
MIM
147851
*RECORD*
*FIELD* NO
147851
*FIELD* TI
*147851 INTERLEUKIN 5 RECEPTOR, ALPHA; IL5RA
;;IL5R
*FIELD* TX
CLONING
Tavernier et al. (1991) isolated cDNA clones encoding 2 receptor
read moreproteins involved in the binding of human interleukin-5 (IL5; 147850).
The major transcript of this receptor gene, as analyzed in both
eosinophilic sublines of human promyelocytic cells and in eosinophilic
myelocytes grown from cord blood, encodes a secreted form of this
receptor. A second component of the receptor was found to be identical
to the beta chain of the human granulocyte-macrophage colony-stimulating
factor high affinity receptor (CSF2RB; 138981). The finding that IL5 and
CSF2 share a receptor subunit provides a molecular basis for the
observation that these cytokines can partially interfere with each
other's binding and have highly overlapping biologic activities on
eosinophils. The common use of the same receptor component is
reminiscent of the structural relatedness of IL3 (147740), IL5, and
GM-CSF (CSF2; 138960). The homology at the C terminus may indicate a
related binding domain. The common origin of all 3 cytokines is also
suggested by their clustered chromosomal localization and by the
structure of their genes.
The 60-kD alpha chain binds IL5; the 130-kD beta chain increases the
binding affinity but cannot bind IL5 by itself. In addition, the beta
chain is required for signal transduction, most likely by association
with other receptor components. Tavernier et al. (1992) demonstrated
that soluble isoforms of the alpha subunit result from a 'normal'
splicing event or from the absence of splicing, whereas synthesis of
membrane-anchored forms of the alpha subunit requires alternative
splicing.
GENE FUNCTION
Using a yeast 2-hybrid screen of a granulocyte cDNA library with the
cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an
interaction of IL5RA with syntenin (SDCBP; 602217). GST pull-down,
BIAcore, coimmunoprecipitation, and deletion mutant analyses confirmed
an association of syntenin with the last 15 C-terminal residues of
IL5RA; syntenin did not interact with CFS2RB. Within this 15-residue
stretch of IL5RA, the C-terminal phenylalanine is critical. Deletion of
either of the 2 tandem PDZ domains of syntenin, which are known to
interact with C-terminal peptide sequences, abrogated the IL5RA-syntenin
interaction. A second 2-hybrid screen identified the mouse
transcriptional factor Sox4 (184430) as a binding partner for syntenin
but not for IL5RA. The syntenin-Sox4 interaction occurs outside of the
PDZ domains of syntenin. Luciferase reporter analysis and fluorescence
microscopy showed that IL5, but not IL3, induces cytoplasmic and nuclear
expression of syntenin and, in a syntenin- and cytoplasmic
IL5RA-dependent manner, of Sox4. Geijsen et al. (2001) concluded that
syntenin acts as an adaptor molecule in the IL5RA-mediated activation of
SOX4. They also noted that mice lacking either Il5ra or Sox4 have
defects in B-cell development.
GENE STRUCTURE
Sun et al. (1995) identified a promoter (P1) located 5-prime upstream of
exon 1 of the IL5RA gene. Zhang et al. (1997) showed that an additional
promoter (P2) was present in the 5-prime upstream region of exon 2 of
the IL5RA gene.
MAPPING
By use of recombinant inbred strains of mice, Gough and Rakar (1992)
localized the murine equivalent of the IL5R gene to the distal half of
chromosome 6. The position lay between 2 regions of conserved synteny,
one on human chromosome 2 and the second on human chromosome 3. The
human IL5R gene presumably maps to one of these 2 chromosomes. Isobe et
al. (1992) mapped the IL5RA gene to 3p26-p24 by Southern blot analysis
of DNA from a panel of mouse-human hybrid somatic cell lines
complemented by in situ hybridization. Jacob et al. (1993) assigned the
IL5R gene to 3p26-p25 by study of human-rodent somatic cell hybrids
containing various portions of human chromosome 3 and using a
human-specific IL5R tandem repeat marker. Using the mouse-specific
tandem repeat marker in recombinant inbred strains of mice, they
assigned the Il5r gene to the distal part of mouse chromosome 6, close
to the Raf1 locus.
*FIELD* RF
1. Geijsen, N.; Uings, I. J.; Pals, C.; Armstrong, J.; McKinnon, M.;
Raaijmakers, J. A. M.; Lammers, J.-W. J.; Koenderman, L.; Coffer,
P. J.: Cytokine-specific transcriptional regulation through an IL-5R-alpha
interacting protein. Science 293: 1136-1138, 2001.
2. Gough, N. M.; Rakar, S.: Localization of the IL-5 receptor gene
to the distal half of murine chromosome 6 using recombinant inbred
strains of mice. Genomics 12: 855-856, 1992.
3. Isobe, M.; Kumura, Y.; Murata, Y.; Takaki, S.; Tominaga, A.; Takatsu,
K.; Ogita, Z.: Localization of the gene encoding the alpha subunit
of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26. Genomics 14:
755-758, 1992.
4. Jacob, C. O.; Mykytyn, K.; Varcony, T.; Drabkin, H. A.: Mapping
of the interleukin 5 receptor gene to human chromosome 3p25-p26 and
to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem
repeat sequences. Mammalian Genome 4: 435-439, 1993.
5. Sun, Z.; Yergeau, D. A.; Tuypens, T.; Tavernier, J.; Paul, C. C.;
Baumann, M. A.: Tenen, D. G.; Ackerman, S. J.: Identification and
characterization of a functional promoter region in the human eosinophil
IL-5 receptor alpha subunit gene. J. Biol. Chem. 270: 1462-1471,
1995.
6. Tavernier, J.; Devos, R.; Cornelis, S.; Tuypens, T.; Van der Heyden,
J.; Fiers, W.; Plaetinck, G.: A human high affinity interleukin-5
receptor (IL5R) is composed of an IL5-specific alpha chain and a beta
chain shared with the receptor for GM-CSF. Cell 66: 1175-1184, 1991.
7. Tavernier, J.; Tuypens, T.; Plaetinck, G.; Verhee, A.; Fiers, W.;
Devos, R.: Molecular basis of the membrane-anchored and two soluble
isoforms of the human interleukin 5 receptor alpha subunit. Proc.
Nat. Acad. Sci. 89: 7041-7045, 1992.
8. Zhang, J.; Kuvelkar, R.; Cheewatrakoolpong, B.; Williams, S.; Egan,
R. W.; Billah, M. M.: Evidence for multiple promoters of the human
IL-5 receptor alpha subunit gene: a novel 6-base pair element determines
cell-specific promoter function. J. Immun. 15: 5412-5421, 1997.
*FIELD* CN
Paul J. Converse - updated: 08/16/2001
Victor A. McKusick - updated: 2/10/1999
*FIELD* CD
Victor A. McKusick: 10/4/1991
*FIELD* ED
mgross: 08/16/2001
mgross: 3/10/1999
mgross: 2/16/1999
mgross: 2/15/1999
terry: 2/10/1999
carol: 1/29/1999
dkim: 7/2/1998
terry: 5/13/1994
carol: 8/31/1993
carol: 12/21/1992
carol: 11/5/1992
carol: 8/31/1992
carol: 4/1/1992
*RECORD*
*FIELD* NO
147851
*FIELD* TI
*147851 INTERLEUKIN 5 RECEPTOR, ALPHA; IL5RA
;;IL5R
*FIELD* TX
CLONING
Tavernier et al. (1991) isolated cDNA clones encoding 2 receptor
read moreproteins involved in the binding of human interleukin-5 (IL5; 147850).
The major transcript of this receptor gene, as analyzed in both
eosinophilic sublines of human promyelocytic cells and in eosinophilic
myelocytes grown from cord blood, encodes a secreted form of this
receptor. A second component of the receptor was found to be identical
to the beta chain of the human granulocyte-macrophage colony-stimulating
factor high affinity receptor (CSF2RB; 138981). The finding that IL5 and
CSF2 share a receptor subunit provides a molecular basis for the
observation that these cytokines can partially interfere with each
other's binding and have highly overlapping biologic activities on
eosinophils. The common use of the same receptor component is
reminiscent of the structural relatedness of IL3 (147740), IL5, and
GM-CSF (CSF2; 138960). The homology at the C terminus may indicate a
related binding domain. The common origin of all 3 cytokines is also
suggested by their clustered chromosomal localization and by the
structure of their genes.
The 60-kD alpha chain binds IL5; the 130-kD beta chain increases the
binding affinity but cannot bind IL5 by itself. In addition, the beta
chain is required for signal transduction, most likely by association
with other receptor components. Tavernier et al. (1992) demonstrated
that soluble isoforms of the alpha subunit result from a 'normal'
splicing event or from the absence of splicing, whereas synthesis of
membrane-anchored forms of the alpha subunit requires alternative
splicing.
GENE FUNCTION
Using a yeast 2-hybrid screen of a granulocyte cDNA library with the
cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an
interaction of IL5RA with syntenin (SDCBP; 602217). GST pull-down,
BIAcore, coimmunoprecipitation, and deletion mutant analyses confirmed
an association of syntenin with the last 15 C-terminal residues of
IL5RA; syntenin did not interact with CFS2RB. Within this 15-residue
stretch of IL5RA, the C-terminal phenylalanine is critical. Deletion of
either of the 2 tandem PDZ domains of syntenin, which are known to
interact with C-terminal peptide sequences, abrogated the IL5RA-syntenin
interaction. A second 2-hybrid screen identified the mouse
transcriptional factor Sox4 (184430) as a binding partner for syntenin
but not for IL5RA. The syntenin-Sox4 interaction occurs outside of the
PDZ domains of syntenin. Luciferase reporter analysis and fluorescence
microscopy showed that IL5, but not IL3, induces cytoplasmic and nuclear
expression of syntenin and, in a syntenin- and cytoplasmic
IL5RA-dependent manner, of Sox4. Geijsen et al. (2001) concluded that
syntenin acts as an adaptor molecule in the IL5RA-mediated activation of
SOX4. They also noted that mice lacking either Il5ra or Sox4 have
defects in B-cell development.
GENE STRUCTURE
Sun et al. (1995) identified a promoter (P1) located 5-prime upstream of
exon 1 of the IL5RA gene. Zhang et al. (1997) showed that an additional
promoter (P2) was present in the 5-prime upstream region of exon 2 of
the IL5RA gene.
MAPPING
By use of recombinant inbred strains of mice, Gough and Rakar (1992)
localized the murine equivalent of the IL5R gene to the distal half of
chromosome 6. The position lay between 2 regions of conserved synteny,
one on human chromosome 2 and the second on human chromosome 3. The
human IL5R gene presumably maps to one of these 2 chromosomes. Isobe et
al. (1992) mapped the IL5RA gene to 3p26-p24 by Southern blot analysis
of DNA from a panel of mouse-human hybrid somatic cell lines
complemented by in situ hybridization. Jacob et al. (1993) assigned the
IL5R gene to 3p26-p25 by study of human-rodent somatic cell hybrids
containing various portions of human chromosome 3 and using a
human-specific IL5R tandem repeat marker. Using the mouse-specific
tandem repeat marker in recombinant inbred strains of mice, they
assigned the Il5r gene to the distal part of mouse chromosome 6, close
to the Raf1 locus.
*FIELD* RF
1. Geijsen, N.; Uings, I. J.; Pals, C.; Armstrong, J.; McKinnon, M.;
Raaijmakers, J. A. M.; Lammers, J.-W. J.; Koenderman, L.; Coffer,
P. J.: Cytokine-specific transcriptional regulation through an IL-5R-alpha
interacting protein. Science 293: 1136-1138, 2001.
2. Gough, N. M.; Rakar, S.: Localization of the IL-5 receptor gene
to the distal half of murine chromosome 6 using recombinant inbred
strains of mice. Genomics 12: 855-856, 1992.
3. Isobe, M.; Kumura, Y.; Murata, Y.; Takaki, S.; Tominaga, A.; Takatsu,
K.; Ogita, Z.: Localization of the gene encoding the alpha subunit
of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26. Genomics 14:
755-758, 1992.
4. Jacob, C. O.; Mykytyn, K.; Varcony, T.; Drabkin, H. A.: Mapping
of the interleukin 5 receptor gene to human chromosome 3p25-p26 and
to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem
repeat sequences. Mammalian Genome 4: 435-439, 1993.
5. Sun, Z.; Yergeau, D. A.; Tuypens, T.; Tavernier, J.; Paul, C. C.;
Baumann, M. A.: Tenen, D. G.; Ackerman, S. J.: Identification and
characterization of a functional promoter region in the human eosinophil
IL-5 receptor alpha subunit gene. J. Biol. Chem. 270: 1462-1471,
1995.
6. Tavernier, J.; Devos, R.; Cornelis, S.; Tuypens, T.; Van der Heyden,
J.; Fiers, W.; Plaetinck, G.: A human high affinity interleukin-5
receptor (IL5R) is composed of an IL5-specific alpha chain and a beta
chain shared with the receptor for GM-CSF. Cell 66: 1175-1184, 1991.
7. Tavernier, J.; Tuypens, T.; Plaetinck, G.; Verhee, A.; Fiers, W.;
Devos, R.: Molecular basis of the membrane-anchored and two soluble
isoforms of the human interleukin 5 receptor alpha subunit. Proc.
Nat. Acad. Sci. 89: 7041-7045, 1992.
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*FIELD* CN
Paul J. Converse - updated: 08/16/2001
Victor A. McKusick - updated: 2/10/1999
*FIELD* CD
Victor A. McKusick: 10/4/1991
*FIELD* ED
mgross: 08/16/2001
mgross: 3/10/1999
mgross: 2/16/1999
mgross: 2/15/1999
terry: 2/10/1999
carol: 1/29/1999
dkim: 7/2/1998
terry: 5/13/1994
carol: 8/31/1993
carol: 12/21/1992
carol: 11/5/1992
carol: 8/31/1992
carol: 4/1/1992