Full text data of CSF2RB
CSF2RB
(IL3RB, IL5RB)
[Confidence: high (a blood group or CD marker)]
Cytokine receptor common subunit beta (CDw131; GM-CSF/IL-3/IL-5 receptor common beta subunit; CD131; Flags: Precursor)
Cytokine receptor common subunit beta (CDw131; GM-CSF/IL-3/IL-5 receptor common beta subunit; CD131; Flags: Precursor)
UniProt
P32927
ID IL3RB_HUMAN Reviewed; 897 AA.
AC P32927; Q5JZI1; Q6ICE0;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Cytokine receptor common subunit beta;
DE AltName: Full=CDw131;
DE AltName: Full=GM-CSF/IL-3/IL-5 receptor common beta subunit;
DE AltName: CD_antigen=CD131;
DE Flags: Precursor;
GN Name=CSF2RB; Synonyms=IL3RB, IL5RB;
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 1).
RX PubMed=1702217; DOI=10.1073/pnas.87.24.9655;
RA Hayashida K., Kitamura T., Gorman D.M., Arai K., Yokota T.,
RA Miyajima A.;
RT "Molecular cloning of a second subunit of the receptor for human
RT granulocyte-macrophage colony-stimulating factor (GM-CSF):
RT reconstitution of a high-affinity GM-CSF receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9655-9659(1990).
RN [2]
RP SEQUENCE REVISION TO 454.
RA Kitamura T.;
RL Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH TMEM102.
RX PubMed=17828305; DOI=10.1038/sj.onc.1210778;
RA Kao C.J., Chiang Y.J., Chen P.H., Lin K.R., Hwang P.I., Yang-Yen H.F.,
RA Yen J.J.;
RT "CBAP interacts with the un-liganded common beta-subunit of the GM-
RT CSF/IL-3/IL-5 receptor and induces apoptosis via mitochondrial
RT dysfunction.";
RL Oncogene 27:1397-1403(2008).
RN [7]
RP INVOLVEMENT IN SMDP5.
RX PubMed=21075760; DOI=10.1136/jmg.2010.082586;
RA Tanaka T., Motoi N., Tsuchihashi Y., Tazawa R., Kaneko C., Nei T.,
RA Yamamoto T., Hayashi T., Tagawa T., Nagayasu T., Kuribayashi F.,
RA Ariyoshi K., Nakata K., Morimoto K.;
RT "Adult-onset hereditary pulmonary alveolar proteinosis caused by a
RT single-base deletion in CSF2RB.";
RL J. Med. Genet. 48:205-209(2011).
RN [8]
RP STRUCTURE BY NMR OF 338-438.
RX PubMed=10736232; DOI=10.1006/jmbi.2000.3610;
RA Mulhern T.D., Lopez A.F., D'Andrea R.J., Gaunt C., Vandeleur L.,
RA Vadas M.A., Booker G.W., Bagley C.J.;
RT "The solution structure of the cytokine-binding domain of the common
RT beta-chain of the receptors for granulocyte-macrophage colony-
RT stimulating factor, interleukin-3 and interleukin-5.";
RL J. Mol. Biol. 297:989-1001(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 338-438.
RX PubMed=10753826;
RA Rossjohn J., McKinstry W.J., Woodcock J.M., McClure B.J., Hercus T.R.,
RA Parker M.W., Lopez A.F., Bagley C.J.;
RT "Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor
RT common beta-chain bound to an antagonist.";
RL Blood 95:2491-2498(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-437.
RX PubMed=11207369; DOI=10.1016/S0092-8674(01)00213-6;
RA Carr P.D., Gustin S.E., Church A.P., Murphy J.M., Ford S.C.,
RA Mann D.A., Woltring D.M., Walker I., Ollis D.L., Young I.G.;
RT "Structure of the complete extracellular domain of the common beta
RT subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel
RT dimer configuration.";
RL Cell 104:291-300(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 25-443, DISULFIDE BONDS,
RP SUBUNIT, AND GLYCOSYLATION AT ASN-58 AND ASN-191.
RX PubMed=16754968; DOI=10.1107/S1744309106016812;
RA Carr P.D., Conlan F., Ford S., Ollis D.L., Young I.G.;
RT "An improved resolution structure of the human beta common receptor
RT involved in IL-3, IL-5 and GM-CSF signalling which gives better
RT definition of the high-affinity binding epitope.";
RL Acta Crystallogr. F 62:509-513(2006).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-438 IN COMPLEX WITH CSF2RA
RP AND CSF2, SUBUNIT, GLYCOSYLATION AT ASN-58 AND ASN-191, AND DISULFIDE
RP BONDS.
RX PubMed=18692472; DOI=10.1016/j.cell.2008.05.053;
RA Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M.,
RA Powell J., Ramshaw H., Woodcock J.M., Xu Y., Guthridge M.,
RA McKinstry W.J., Lopez A.F., Parker M.W.;
RT "The structure of the GM-CSF receptor complex reveals a distinct mode
RT of cytokine receptor activation.";
RL Cell 134:496-507(2008).
RN [13]
RP VARIANT THR-603.
RX PubMed=9410898; DOI=10.1172/JCI119758;
RA Dirksen U., Nishinakamura R., Groneck P., Hattenhorst U., Nogee L.,
RA Murray R., Burdach S.;
RT "Human pulmonary alveolar proteinosis associated with a defect in GM-
RT CSF/IL-3/IL-5 receptor common beta chain expression.";
RL J. Clin. Invest. 100:2211-2217(1997).
CC -!- FUNCTION: High affinity receptor for interleukin-3, interleukin-5
CC and granulocyte-macrophage colony-stimulating factor.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The beta
CC subunit is common to the IL3, IL5 and GM-CSF receptors. The
CC signaling GM-CSF receptor complex is a dodecamer of two head-to-
CC head hexamers of two alpha, two beta, and two ligand subunits.
CC Interacts with TMEM102; this interaction occurs preferentially in
CC the absence of CSF2. Interacts with LYN (By similarity).
CC -!- INTERACTION:
CC P04141:CSF2; NbExp=2; IntAct=EBI-1809771, EBI-1809826;
CC P05113:IL5; NbExp=2; IntAct=EBI-1809771, EBI-2435811;
CC P05556:ITGB1; NbExp=5; IntAct=EBI-1809771, EBI-703066;
CC O60674:JAK2; NbExp=4; IntAct=EBI-1809771, EBI-518647;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32927-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32927-2; Sequence=VSP_032798;
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 -!- PTM: May be phosphorylated by LYN (By similarity).
CC -!- DISEASE: Pulmonary surfactant metabolism dysfunction 5 (SMDP5)
CC [MIM:614370]: A rare lung disorder due to impaired surfactant
CC homeostasis. It is characterized by alveolar filling with
CC floccular material that stains positive using the periodic acid-
CC Schiff method and is derived from surfactant phospholipids and
CC protein components. Excessive lipoproteins accumulation in the
CC alveoli results in severe respiratory distress. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 4
CC subfamily.
CC -!- SIMILARITY: Contains 2 fibronectin type-III domains.
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DR EMBL; M59941; AAA18171.1; -; mRNA.
DR EMBL; CR456428; CAG30314.1; -; mRNA.
DR EMBL; AL008637; CAI17999.1; -; Genomic_DNA.
DR EMBL; AL133392; CAI17999.1; JOINED; Genomic_DNA.
DR EMBL; AL008637; CAQ10744.1; -; Genomic_DNA.
DR EMBL; AL133392; CAQ10744.1; JOINED; Genomic_DNA.
DR EMBL; CH471095; EAW60125.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW60126.1; -; Genomic_DNA.
DR PIR; A39255; A39255.
DR RefSeq; NP_000386.1; NM_000395.2.
DR RefSeq; XP_005261397.1; XM_005261340.1.
DR UniGene; Hs.592192; -.
DR PDB; 1C8P; NMR; -; A=338-438.
DR PDB; 1EGJ; X-ray; 2.80 A; A=338-438.
DR PDB; 1GH7; X-ray; 3.00 A; A/B=25-437.
DR PDB; 2GYS; X-ray; 2.70 A; A/B=25-437.
DR PDB; 3CXE; X-ray; 3.30 A; A=25-438.
DR PDBsum; 1C8P; -.
DR PDBsum; 1EGJ; -.
DR PDBsum; 1GH7; -.
DR PDBsum; 2GYS; -.
DR PDBsum; 3CXE; -.
DR ProteinModelPortal; P32927; -.
DR SMR; P32927; 25-438.
DR DIP; DIP-127N; -.
DR IntAct; P32927; 14.
DR MINT; MINT-105697; -.
DR STRING; 9606.ENSP00000384053; -.
DR ChEMBL; CHEMBL2364169; -.
DR DrugBank; DB00020; Sargramostim.
DR PhosphoSite; P32927; -.
DR DMDM; 1345923; -.
DR PaxDb; P32927; -.
DR PRIDE; P32927; -.
DR DNASU; 1439; -.
DR Ensembl; ENST00000262825; ENSP00000262825; ENSG00000100368.
DR Ensembl; ENST00000403662; ENSP00000384053; ENSG00000100368.
DR Ensembl; ENST00000406230; ENSP00000385271; ENSG00000100368.
DR GeneID; 1439; -.
DR KEGG; hsa:1439; -.
DR UCSC; uc003aqa.4; human.
DR CTD; 1439; -.
DR GeneCards; GC22P037309; -.
DR HGNC; HGNC:2436; CSF2RB.
DR HPA; CAB010251; -.
DR MIM; 138981; gene.
DR MIM; 614370; phenotype.
DR neXtProt; NX_P32927; -.
DR Orphanet; 264675; Congenital pulmonary alveolar proteinosis.
DR PharmGKB; PA26939; -.
DR eggNOG; NOG39324; -.
DR HOGENOM; HOG000113049; -.
DR HOVERGEN; HBG052113; -.
DR KO; K04738; -.
DR OMA; CRWADTQ; -.
DR OrthoDB; EOG7966FT; -.
DR PhylomeDB; P32927; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P32927; -.
DR EvolutionaryTrace; P32927; -.
DR GenomeRNAi; 1439; -.
DR NextBio; 5889; -.
DR PRO; PR:P32927; -.
DR ArrayExpress; P32927; -.
DR Bgee; P32927; -.
DR CleanEx; HS_CSF2RB; -.
DR Genevestigator; P32927; -.
DR GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; TAS:UniProtKB.
DR GO; GO:0004896; F:cytokine receptor activity; IEA:InterPro.
DR GO; GO:0004872; F:receptor activity; TAS:ProtInc.
DR GO; GO:0036016; P:cellular response to interleukin-3; TAS:GOC.
DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; TAS:GOC.
DR GO; GO:0038043; P:interleukin-5-mediated signaling pathway; TAS:GOC.
DR GO; GO:0007585; P:respiratory gaseous exchange; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR003531; Hempt_rcpt_S_F1_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015321; IL-6_rcpt_alpha-bd.
DR InterPro; IPR011365; IL3_rcpt_beta.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF09240; IL6Ra-bind; 1.
DR PIRSF; PIRSF001956; IL3R_beta_c; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01355; HEMATOPO_REC_S_F1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Polymorphism; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 16 Potential.
FT CHAIN 17 897 Cytokine receptor common subunit beta.
FT /FTId=PRO_0000010862.
FT TOPO_DOM 17 443 Extracellular (Potential).
FT TRANSMEM 444 460 Helical; (Potential).
FT TOPO_DOM 461 897 Cytoplasmic (Potential).
FT DOMAIN 133 240 Fibronectin type-III 1.
FT DOMAIN 339 436 Fibronectin type-III 2.
FT MOTIF 425 429 WSXWS motif.
FT MOTIF 474 482 Box 1 motif.
FT MOD_RES 766 766 Phosphotyrosine (By similarity).
FT CARBOHYD 58 58 N-linked (GlcNAc...).
FT CARBOHYD 191 191 N-linked (GlcNAc...).
FT CARBOHYD 346 346 N-linked (GlcNAc...) (Potential).
FT DISULFID 35 45
FT DISULFID 75 96
FT DISULFID 86 91
FT DISULFID 250 260
FT DISULFID 289 306
FT VAR_SEQ 285 285 G -> GSAVLLR (in isoform 2).
FT /FTId=VSP_032798.
FT VARIANT 249 249 E -> Q (in dbSNP:rs16845).
FT /FTId=VAR_042521.
FT VARIANT 603 603 P -> T (in dbSNP:rs1801122).
FT /FTId=VAR_014801.
FT VARIANT 647 647 G -> V (in dbSNP:rs1801115).
FT /FTId=VAR_014802.
FT VARIANT 652 652 V -> M (in dbSNP:rs1801114).
FT /FTId=VAR_014803.
FT VARIANT 696 696 P -> S (in dbSNP:rs16997517).
FT /FTId=VAR_042522.
FT HELIX 28 32
FT STRAND 34 37
FT STRAND 39 50
FT HELIX 51 54
FT STRAND 59 66
FT STRAND 69 72
FT STRAND 75 77
FT STRAND 88 99
FT STRAND 108 117
FT STRAND 121 126
FT HELIX 127 129
FT STRAND 137 144
FT STRAND 147 153
FT HELIX 166 168
FT STRAND 169 177
FT HELIX 182 184
FT STRAND 186 197
FT TURN 199 201
FT STRAND 207 216
FT STRAND 218 221
FT STRAND 233 236
FT STRAND 242 244
FT STRAND 246 252
FT STRAND 254 265
FT HELIX 266 269
FT STRAND 274 279
FT STRAND 292 295
FT TURN 298 300
FT STRAND 301 309
FT TURN 313 315
FT STRAND 318 325
FT STRAND 330 333
FT HELIX 334 336
FT STRAND 337 339
FT STRAND 344 348
FT STRAND 350 352
FT STRAND 355 359
FT STRAND 365 367
FT STRAND 370 377
FT STRAND 379 381
FT HELIX 383 385
FT STRAND 388 393
FT STRAND 395 398
FT STRAND 405 407
FT STRAND 409 416
FT STRAND 418 420
FT STRAND 432 436
SQ SEQUENCE 897 AA; 97336 MW; 3398E37FDB8F393A CRC64;
MVLAQGLLSM ALLALCWERS LAGAEETIPL QTLRCYNDYT SHITCRWADT QDAQRLVNVT
LIRRVNEDLL EPVSCDLSDD MPWSACPHPR CVPRRCVIPC QSFVVTDVDY FSFQPDRPLG
TRLTVTLTQH VQPPEPRDLQ ISTDQDHFLL TWSVALGSPQ SHWLSPGDLE FEVVYKRLQD
SWEDAAILLS NTSQATLGPE HLMPSSTYVA RVRTRLAPGS RLSGRPSKWS PEVCWDSQPG
DEAQPQNLEC FFDGAAVLSC SWEVRKEVAS SVSFGLFYKP SPDAGEEECS PVLREGLGSL
HTRHHCQIPV PDPATHGQYI VSVQPRRAEK HIKSSVNIQM APPSLNVTKD GDSYSLRWET
MKMRYEHIDH TFEIQYRKDT ATWKDSKTET LQNAHSMALP ALEPSTRYWA RVRVRTSRTG
YNGIWSEWSE ARSWDTESVL PMWVLALIVI FLTIAVLLAL RFCGIYGYRL RRKWEEKIPN
PSKSHLFQNG SAELWPPGSM SAFTSGSPPH QGPWGSRFPE LEGVFPVGFG DSEVSPLTIE
DPKHVCDPPS GPDTTPAASD LPTEQPPSPQ PGPPAASHTP EKQASSFDFN GPYLGPPHSR
SLPDILGQPE PPQEGGSQKS PPPGSLEYLC LPAGGQVQLV PLAQAMGPGQ AVEVERRPSQ
GAAGSPSLES GGGPAPPALG PRVGGQDQKD SPVAIPMSSG DTEDPGVASG YVSSADLVFT
PNSGASSVSL VPSLGLPSDQ TPSLCPGLAS GPPGAPGPVK SGFEGYVELP PIEGRSPRSP
RNNPVPPEAK SPVLNPGERP ADVSPTSPQP EGLLVLQQVG DYCFLPGLGP GPLSLRSKPS
SPGPGPEIKN LDQAFQVKKP PGQAVPQVPV IQLFKALKQQ DYLSLPPWEV NKPGEVC
//
ID IL3RB_HUMAN Reviewed; 897 AA.
AC P32927; Q5JZI1; Q6ICE0;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Cytokine receptor common subunit beta;
DE AltName: Full=CDw131;
DE AltName: Full=GM-CSF/IL-3/IL-5 receptor common beta subunit;
DE AltName: CD_antigen=CD131;
DE Flags: Precursor;
GN Name=CSF2RB; Synonyms=IL3RB, IL5RB;
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 1).
RX PubMed=1702217; DOI=10.1073/pnas.87.24.9655;
RA Hayashida K., Kitamura T., Gorman D.M., Arai K., Yokota T.,
RA Miyajima A.;
RT "Molecular cloning of a second subunit of the receptor for human
RT granulocyte-macrophage colony-stimulating factor (GM-CSF):
RT reconstitution of a high-affinity GM-CSF receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9655-9659(1990).
RN [2]
RP SEQUENCE REVISION TO 454.
RA Kitamura T.;
RL Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH TMEM102.
RX PubMed=17828305; DOI=10.1038/sj.onc.1210778;
RA Kao C.J., Chiang Y.J., Chen P.H., Lin K.R., Hwang P.I., Yang-Yen H.F.,
RA Yen J.J.;
RT "CBAP interacts with the un-liganded common beta-subunit of the GM-
RT CSF/IL-3/IL-5 receptor and induces apoptosis via mitochondrial
RT dysfunction.";
RL Oncogene 27:1397-1403(2008).
RN [7]
RP INVOLVEMENT IN SMDP5.
RX PubMed=21075760; DOI=10.1136/jmg.2010.082586;
RA Tanaka T., Motoi N., Tsuchihashi Y., Tazawa R., Kaneko C., Nei T.,
RA Yamamoto T., Hayashi T., Tagawa T., Nagayasu T., Kuribayashi F.,
RA Ariyoshi K., Nakata K., Morimoto K.;
RT "Adult-onset hereditary pulmonary alveolar proteinosis caused by a
RT single-base deletion in CSF2RB.";
RL J. Med. Genet. 48:205-209(2011).
RN [8]
RP STRUCTURE BY NMR OF 338-438.
RX PubMed=10736232; DOI=10.1006/jmbi.2000.3610;
RA Mulhern T.D., Lopez A.F., D'Andrea R.J., Gaunt C., Vandeleur L.,
RA Vadas M.A., Booker G.W., Bagley C.J.;
RT "The solution structure of the cytokine-binding domain of the common
RT beta-chain of the receptors for granulocyte-macrophage colony-
RT stimulating factor, interleukin-3 and interleukin-5.";
RL J. Mol. Biol. 297:989-1001(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 338-438.
RX PubMed=10753826;
RA Rossjohn J., McKinstry W.J., Woodcock J.M., McClure B.J., Hercus T.R.,
RA Parker M.W., Lopez A.F., Bagley C.J.;
RT "Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor
RT common beta-chain bound to an antagonist.";
RL Blood 95:2491-2498(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-437.
RX PubMed=11207369; DOI=10.1016/S0092-8674(01)00213-6;
RA Carr P.D., Gustin S.E., Church A.P., Murphy J.M., Ford S.C.,
RA Mann D.A., Woltring D.M., Walker I., Ollis D.L., Young I.G.;
RT "Structure of the complete extracellular domain of the common beta
RT subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel
RT dimer configuration.";
RL Cell 104:291-300(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 25-443, DISULFIDE BONDS,
RP SUBUNIT, AND GLYCOSYLATION AT ASN-58 AND ASN-191.
RX PubMed=16754968; DOI=10.1107/S1744309106016812;
RA Carr P.D., Conlan F., Ford S., Ollis D.L., Young I.G.;
RT "An improved resolution structure of the human beta common receptor
RT involved in IL-3, IL-5 and GM-CSF signalling which gives better
RT definition of the high-affinity binding epitope.";
RL Acta Crystallogr. F 62:509-513(2006).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-438 IN COMPLEX WITH CSF2RA
RP AND CSF2, SUBUNIT, GLYCOSYLATION AT ASN-58 AND ASN-191, AND DISULFIDE
RP BONDS.
RX PubMed=18692472; DOI=10.1016/j.cell.2008.05.053;
RA Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M.,
RA Powell J., Ramshaw H., Woodcock J.M., Xu Y., Guthridge M.,
RA McKinstry W.J., Lopez A.F., Parker M.W.;
RT "The structure of the GM-CSF receptor complex reveals a distinct mode
RT of cytokine receptor activation.";
RL Cell 134:496-507(2008).
RN [13]
RP VARIANT THR-603.
RX PubMed=9410898; DOI=10.1172/JCI119758;
RA Dirksen U., Nishinakamura R., Groneck P., Hattenhorst U., Nogee L.,
RA Murray R., Burdach S.;
RT "Human pulmonary alveolar proteinosis associated with a defect in GM-
RT CSF/IL-3/IL-5 receptor common beta chain expression.";
RL J. Clin. Invest. 100:2211-2217(1997).
CC -!- FUNCTION: High affinity receptor for interleukin-3, interleukin-5
CC and granulocyte-macrophage colony-stimulating factor.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The beta
CC subunit is common to the IL3, IL5 and GM-CSF receptors. The
CC signaling GM-CSF receptor complex is a dodecamer of two head-to-
CC head hexamers of two alpha, two beta, and two ligand subunits.
CC Interacts with TMEM102; this interaction occurs preferentially in
CC the absence of CSF2. Interacts with LYN (By similarity).
CC -!- INTERACTION:
CC P04141:CSF2; NbExp=2; IntAct=EBI-1809771, EBI-1809826;
CC P05113:IL5; NbExp=2; IntAct=EBI-1809771, EBI-2435811;
CC P05556:ITGB1; NbExp=5; IntAct=EBI-1809771, EBI-703066;
CC O60674:JAK2; NbExp=4; IntAct=EBI-1809771, EBI-518647;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32927-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32927-2; Sequence=VSP_032798;
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 -!- PTM: May be phosphorylated by LYN (By similarity).
CC -!- DISEASE: Pulmonary surfactant metabolism dysfunction 5 (SMDP5)
CC [MIM:614370]: A rare lung disorder due to impaired surfactant
CC homeostasis. It is characterized by alveolar filling with
CC floccular material that stains positive using the periodic acid-
CC Schiff method and is derived from surfactant phospholipids and
CC protein components. Excessive lipoproteins accumulation in the
CC alveoli results in severe respiratory distress. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 4
CC subfamily.
CC -!- SIMILARITY: Contains 2 fibronectin type-III domains.
CC -----------------------------------------------------------------------
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DR EMBL; M59941; AAA18171.1; -; mRNA.
DR EMBL; CR456428; CAG30314.1; -; mRNA.
DR EMBL; AL008637; CAI17999.1; -; Genomic_DNA.
DR EMBL; AL133392; CAI17999.1; JOINED; Genomic_DNA.
DR EMBL; AL008637; CAQ10744.1; -; Genomic_DNA.
DR EMBL; AL133392; CAQ10744.1; JOINED; Genomic_DNA.
DR EMBL; CH471095; EAW60125.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW60126.1; -; Genomic_DNA.
DR PIR; A39255; A39255.
DR RefSeq; NP_000386.1; NM_000395.2.
DR RefSeq; XP_005261397.1; XM_005261340.1.
DR UniGene; Hs.592192; -.
DR PDB; 1C8P; NMR; -; A=338-438.
DR PDB; 1EGJ; X-ray; 2.80 A; A=338-438.
DR PDB; 1GH7; X-ray; 3.00 A; A/B=25-437.
DR PDB; 2GYS; X-ray; 2.70 A; A/B=25-437.
DR PDB; 3CXE; X-ray; 3.30 A; A=25-438.
DR PDBsum; 1C8P; -.
DR PDBsum; 1EGJ; -.
DR PDBsum; 1GH7; -.
DR PDBsum; 2GYS; -.
DR PDBsum; 3CXE; -.
DR ProteinModelPortal; P32927; -.
DR SMR; P32927; 25-438.
DR DIP; DIP-127N; -.
DR IntAct; P32927; 14.
DR MINT; MINT-105697; -.
DR STRING; 9606.ENSP00000384053; -.
DR ChEMBL; CHEMBL2364169; -.
DR DrugBank; DB00020; Sargramostim.
DR PhosphoSite; P32927; -.
DR DMDM; 1345923; -.
DR PaxDb; P32927; -.
DR PRIDE; P32927; -.
DR DNASU; 1439; -.
DR Ensembl; ENST00000262825; ENSP00000262825; ENSG00000100368.
DR Ensembl; ENST00000403662; ENSP00000384053; ENSG00000100368.
DR Ensembl; ENST00000406230; ENSP00000385271; ENSG00000100368.
DR GeneID; 1439; -.
DR KEGG; hsa:1439; -.
DR UCSC; uc003aqa.4; human.
DR CTD; 1439; -.
DR GeneCards; GC22P037309; -.
DR HGNC; HGNC:2436; CSF2RB.
DR HPA; CAB010251; -.
DR MIM; 138981; gene.
DR MIM; 614370; phenotype.
DR neXtProt; NX_P32927; -.
DR Orphanet; 264675; Congenital pulmonary alveolar proteinosis.
DR PharmGKB; PA26939; -.
DR eggNOG; NOG39324; -.
DR HOGENOM; HOG000113049; -.
DR HOVERGEN; HBG052113; -.
DR KO; K04738; -.
DR OMA; CRWADTQ; -.
DR OrthoDB; EOG7966FT; -.
DR PhylomeDB; P32927; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P32927; -.
DR EvolutionaryTrace; P32927; -.
DR GenomeRNAi; 1439; -.
DR NextBio; 5889; -.
DR PRO; PR:P32927; -.
DR ArrayExpress; P32927; -.
DR Bgee; P32927; -.
DR CleanEx; HS_CSF2RB; -.
DR Genevestigator; P32927; -.
DR GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; TAS:UniProtKB.
DR GO; GO:0004896; F:cytokine receptor activity; IEA:InterPro.
DR GO; GO:0004872; F:receptor activity; TAS:ProtInc.
DR GO; GO:0036016; P:cellular response to interleukin-3; TAS:GOC.
DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; TAS:GOC.
DR GO; GO:0038043; P:interleukin-5-mediated signaling pathway; TAS:GOC.
DR GO; GO:0007585; P:respiratory gaseous exchange; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR003531; Hempt_rcpt_S_F1_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015321; IL-6_rcpt_alpha-bd.
DR InterPro; IPR011365; IL3_rcpt_beta.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF09240; IL6Ra-bind; 1.
DR PIRSF; PIRSF001956; IL3R_beta_c; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01355; HEMATOPO_REC_S_F1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Polymorphism; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 16 Potential.
FT CHAIN 17 897 Cytokine receptor common subunit beta.
FT /FTId=PRO_0000010862.
FT TOPO_DOM 17 443 Extracellular (Potential).
FT TRANSMEM 444 460 Helical; (Potential).
FT TOPO_DOM 461 897 Cytoplasmic (Potential).
FT DOMAIN 133 240 Fibronectin type-III 1.
FT DOMAIN 339 436 Fibronectin type-III 2.
FT MOTIF 425 429 WSXWS motif.
FT MOTIF 474 482 Box 1 motif.
FT MOD_RES 766 766 Phosphotyrosine (By similarity).
FT CARBOHYD 58 58 N-linked (GlcNAc...).
FT CARBOHYD 191 191 N-linked (GlcNAc...).
FT CARBOHYD 346 346 N-linked (GlcNAc...) (Potential).
FT DISULFID 35 45
FT DISULFID 75 96
FT DISULFID 86 91
FT DISULFID 250 260
FT DISULFID 289 306
FT VAR_SEQ 285 285 G -> GSAVLLR (in isoform 2).
FT /FTId=VSP_032798.
FT VARIANT 249 249 E -> Q (in dbSNP:rs16845).
FT /FTId=VAR_042521.
FT VARIANT 603 603 P -> T (in dbSNP:rs1801122).
FT /FTId=VAR_014801.
FT VARIANT 647 647 G -> V (in dbSNP:rs1801115).
FT /FTId=VAR_014802.
FT VARIANT 652 652 V -> M (in dbSNP:rs1801114).
FT /FTId=VAR_014803.
FT VARIANT 696 696 P -> S (in dbSNP:rs16997517).
FT /FTId=VAR_042522.
FT HELIX 28 32
FT STRAND 34 37
FT STRAND 39 50
FT HELIX 51 54
FT STRAND 59 66
FT STRAND 69 72
FT STRAND 75 77
FT STRAND 88 99
FT STRAND 108 117
FT STRAND 121 126
FT HELIX 127 129
FT STRAND 137 144
FT STRAND 147 153
FT HELIX 166 168
FT STRAND 169 177
FT HELIX 182 184
FT STRAND 186 197
FT TURN 199 201
FT STRAND 207 216
FT STRAND 218 221
FT STRAND 233 236
FT STRAND 242 244
FT STRAND 246 252
FT STRAND 254 265
FT HELIX 266 269
FT STRAND 274 279
FT STRAND 292 295
FT TURN 298 300
FT STRAND 301 309
FT TURN 313 315
FT STRAND 318 325
FT STRAND 330 333
FT HELIX 334 336
FT STRAND 337 339
FT STRAND 344 348
FT STRAND 350 352
FT STRAND 355 359
FT STRAND 365 367
FT STRAND 370 377
FT STRAND 379 381
FT HELIX 383 385
FT STRAND 388 393
FT STRAND 395 398
FT STRAND 405 407
FT STRAND 409 416
FT STRAND 418 420
FT STRAND 432 436
SQ SEQUENCE 897 AA; 97336 MW; 3398E37FDB8F393A CRC64;
MVLAQGLLSM ALLALCWERS LAGAEETIPL QTLRCYNDYT SHITCRWADT QDAQRLVNVT
LIRRVNEDLL EPVSCDLSDD MPWSACPHPR CVPRRCVIPC QSFVVTDVDY FSFQPDRPLG
TRLTVTLTQH VQPPEPRDLQ ISTDQDHFLL TWSVALGSPQ SHWLSPGDLE FEVVYKRLQD
SWEDAAILLS NTSQATLGPE HLMPSSTYVA RVRTRLAPGS RLSGRPSKWS PEVCWDSQPG
DEAQPQNLEC FFDGAAVLSC SWEVRKEVAS SVSFGLFYKP SPDAGEEECS PVLREGLGSL
HTRHHCQIPV PDPATHGQYI VSVQPRRAEK HIKSSVNIQM APPSLNVTKD GDSYSLRWET
MKMRYEHIDH TFEIQYRKDT ATWKDSKTET LQNAHSMALP ALEPSTRYWA RVRVRTSRTG
YNGIWSEWSE ARSWDTESVL PMWVLALIVI FLTIAVLLAL RFCGIYGYRL RRKWEEKIPN
PSKSHLFQNG SAELWPPGSM SAFTSGSPPH QGPWGSRFPE LEGVFPVGFG DSEVSPLTIE
DPKHVCDPPS GPDTTPAASD LPTEQPPSPQ PGPPAASHTP EKQASSFDFN GPYLGPPHSR
SLPDILGQPE PPQEGGSQKS PPPGSLEYLC LPAGGQVQLV PLAQAMGPGQ AVEVERRPSQ
GAAGSPSLES GGGPAPPALG PRVGGQDQKD SPVAIPMSSG DTEDPGVASG YVSSADLVFT
PNSGASSVSL VPSLGLPSDQ TPSLCPGLAS GPPGAPGPVK SGFEGYVELP PIEGRSPRSP
RNNPVPPEAK SPVLNPGERP ADVSPTSPQP EGLLVLQQVG DYCFLPGLGP GPLSLRSKPS
SPGPGPEIKN LDQAFQVKKP PGQAVPQVPV IQLFKALKQQ DYLSLPPWEV NKPGEVC
//
MIM
138981
*RECORD*
*FIELD* NO
138981
*FIELD* TI
*138981 GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR, BETA; CSF2RB
;;INTERLEUKIN 5 RECEPTOR, BETA; IL5RB;;
read moreINTERLEUKIN 3 RECEPTOR, BETA; IL3RB;;
COMMON BETA CHAIN;;
BETA-C
*FIELD* TX
DESCRIPTION
The CSF2RB gene encodes the high-affinity beta subunit of a receptor for
interleukin-5 (IL5R; 147851), granulocyte-macrophage CSF (CSF2R; 306250)
(Tavernier et al., 1991), and interleukin-3 (IL3RA; 308385) (Kitamura et
al., 1991).
See also the low-affinity alpha subunit of the receptor (CSF2RA; 306250)
CLONING
Hayashida et al. (1990) isolated cDNA clones corresponding to the beta
subunit of the GMCSF receptor from a human erythroleukemia cDNA library.
The deduced 897-amino acid protein had a molecular mass of approximately
120 kD and shares 56% sequence identity with the mouse AIC2B protein.
In the mouse, 2 distinct but related genes, AIC2A (Csf2rb2) and AIC2B
(Csf2rb1), encode the beta subunit common to Csf2r, Il5r, and Il3r
(Gorman et al., 1992). Hara and Miyajima (1992) stated that the mouse
AIC2B gene encodes a common beta subunit for the mouse Gmcsf and Il5
receptors, whereas AIC2A encodes a low-affinity Il3-binding protein by
itself. Hara and Miyajima (1992) found that AIC2A formed a high-affinity
Il3-binding protein when coexpressed with a mouse protein homologous to
the human alpha subunit. In addition, AIC2B formed a high-affinity
Il3-binding protein when coexpressed with the alpha subunit. Thus, the
mouse has 2 high-affinity Il3 receptors, but only the AIC2B gene encodes
a common beta subunit for the mouse Gmcsf, Il5, and Il3 receptors. Robb
et al. (1995) referred to the mouse AIC2B gene as 'beta-c' (for common)
and the AIC2A gene as 'beta-Il3.'
MAPPING
Shen et al. (1992) mapped the human CSF2RB gene to chromosome 22 by PCR
analysis of a series of human/rodent somatic cell hybrids. By
fluorescence in situ hybridization to normal human chromosomes and 2
translocations involving chromosome 22 as well as the chromosome
expressing the rare fragile site FRA22A, they regionalized the gene to
22q12.2-q13.1, proximal to the fragile site.
Gorman et al. (1992) demonstrated that the 2 mouse genes, provisionally
designated Il3rb1 and Il3rb2, are located in the same 250-kb restriction
fragment and map to chromosome 5, closely linked to the Sis locus
(PDGFB; 190040).
GENE FUNCTION
Tavernier et al. (1991) stated that the common receptor subunit, CSF2RB,
that is shared between IL5R and CSF2R provides a molecular basis for the
observation that IL5 (147850) and CSF2 (138960) can partially interfere
with each other's binding and have highly overlapping biologic
activities on eosinophils.
D'Andrea et al. (1994) isolated a mutant form of the IL5RB gene from
growth factor-independent cells that arose spontaneously after infection
of a murine factor-dependent hematopoietic cell line with a retroviral
expression construct of the common beta chain gene. The mutation
consisted of a 37-amino acid duplication of extracellular sequence that
included 2 conserved sequence motifs and conferred ligand-independent
growth on the cells. The results suggested that members of the large
family of cytokine receptors have the capacity to become oncogenically
active.
Jenkins et al. (1995) reported the identification of 2 activating point
mutations in the CSF2RB gene that were generated using a PCR-based
random mutagenesis procedure. By combining this procedure with a
retroviral expression cloning system, they isolated these mutants by
virtue of their ability to confer factor independence on a
factor-dependent hematopoietic cell line. The ability of point mutations
to activate the gene supported the possibility that such mutations could
contribute to human leukemia. In addition, the nature and properties of
these mutants had important implications for the mechanisms of signaling
by the 3 receptors that utilize the common beta subunit. One mutation,
val449-to-glu, was located within the transmembrane domain and, by
analogy with a similar mutation in the NEU oncogene (164870), might act
by inducing dimerization of the common beta subunit. The other mutation,
ile374-to-asn, lay in the extracellular, membrane-proximal portion of
the common beta molecule.
Dirksen et al. (1998) described expression defects of the CSF2RB and/or
the CSF2RA genes in 3 pediatric patients with acute myeloid leukemia
(AML) and pulmonary alveolar proteinosis. Leukemic cells from all 3
patients failed to express express normal levels of beta-c. In addition,
leukemic cells from 2 of the patients lacked expression of CSF2RA, as
shown by flow cytometry. Strikingly reduced or absent function of beta-c
was demonstrated in clonogenic progenitor assays with absent
colony-forming unit growth after GMCSF or IL3 stimulation. The response
to growth factors acting via a growth factor receptor distinct from the
GMCSF/IL3/IL5 system was normal. After antileukemic treatment, the
pulmonary symptoms resolved and beta-c or beta-c plus CSF2RA expression
was normal. Dirksen et al. (1998) concluded that a defect in the CSF2RB
and/or CSF2RA on AML blasts can be associated with respiratory failure
in patients with AML.
Kondo et al. (2000) showed that a clonogenic common lymphoid progenitor,
a bone marrow-resident cell that gives rise exclusively to lymphocytes
(T, B, and natural killer cells), can be redirected to the myeloid
lineage by stimulation through exogenously expressed interleukin-2
receptor (146710) and GMCSF receptor. Analysis of mutants of the beta
chain of the IL2 receptor revealed that the granulocyte and monocyte
differentiation signals are triggered by different cytoplasmic domains,
showing that the signaling pathways responsible for these unique
developmental outcomes are separable. Finally, Kondo et al. (2000)
showed that the endogenous myelomonocytic cytokine receptors for GMCSF
and macrophage colony-stimulating factor (CSF1R; 164770) are expressed
at low to moderate levels on the more primitive hematopoietic stem
cells, are absent on common lymphoid progenitors, and are upregulated
after myeloid lineage induction by IL2 (147680). Kondo et al. (2000)
concluded that cytokine signaling can regulate cell fate decisions and
proposed that a critical step in lymphoid commitment is downregulation
of cytokine receptors that drive myeloid cell development.
Using yeast 2-hybrid, protein pull-down, and coimmunoprecipitation
assays, Kao et al. (2008) showed that CBAP (TMEM102; 613936) interacted
with the box-2 motif of beta-c. Removal of GMCSF increased the amount of
beta-c and CBAP that immunoprecipitated from TF1 erythroleukemia cells
and that colocalized in intracellular compartments. Overexpression of
CBAP in IL3 (147740)-dependent Ba/F3 pro-B cells increased the
percentage of cells showing mitochondrial changes characteristic of
apoptosis and enhanced the apoptotic effect of GMCSF deprivation.
Conversely, knockdown of CBAP in TF1 cells reduced cell sensitivity to
GMCSF deprivation, but not to other proapoptotic stimuli. Kao et al.
(2008) concluded that CBAP binds the isolated beta-c molecule and has a
role in GMCSF deprivation-induced apoptosis.
MOLECULAR GENETICS
Freeburn et al. (1996) failed to find pathogenic mutations in the CSF2RB
gene in 35 patients with acute myeloid leukemia. Although different
patterns were detected in 25 (71%) AML patients and 8 (80%) of 10
healthy controls, all nucleotide changes were found to be polymorphisms.
The authors concluded that the CSF2RB is highly polymorphic, but point
mutations do not appear to contribute to the pathogenesis of AML.
Dirksen et al. (1997) described an expression defect of the CSF2RB gene
in 4 of 7 pediatric patients with pulmonary alveolar proteinosis (see
614370). The patients failed to express normal levels of beta-c, as
shown by flow cytometry. Reduced or absent function of beta-c was
demonstrated by ligand binding studies and progenitor clonogenic assays.
Although molecular analysis of 1 patient identified what the authors
referred to as a pro602-to-thr (P602T) mutation, this change was shown
by Freeburn et al. (1996) to be a polymorphism (P603T with revised
sequence).
In a Japanese woman with adult-onset pulmonary surfactant metabolism
dysfunction-5 (SMDP5; 614370), manifest as pulmonary alveolar
proteinosis, Tanaka et al. (2011) identified a homozygous truncating
mutation in the CSF2RB gene (138981.0001). Each unaffected parent was
heterozygous for the mutation. Tanaka et al. (2011) speculated that the
late onset in this patient may have been due to compensatory factors
such as increased serum GMCSF acting through an intact CSF2RA subunit
(306250) or increased levels of other inflammatory cells.
ANIMAL MODEL
Robb et al. (1995) used gene targeting to create mice with a null
mutation of the common beta subunit of the Csf2rb1 gene (AIC2B). In the
homozygous mice, high-affinity binding of GMCSF (138960) was abolished,
while cells from heterozygous animals showed an intermediate number of
high-affinity receptors. Binding of IL3 (147740) was unaffected,
confirming that the IL3-specific beta-chain remained intact. Homozygous
animals showed reduced eosinophil numbers in peripheral blood and bone
marrow, while other hematologic parameters were normal. In clonal
cultures of homozygous null bone marrow cells, even high concentrations
of GMCSF and IL5 failed to stimulate colony formation, but the cells
exhibited normal quantitative responsiveness to stimulation by IL3 and
other growth factors. The mice exhibited normal development and survived
to young adult life, although they developed pulmonary
peribronchovascular lymphoid infiltrates and areas resembling alveolar
proteinosis. There was no detectable difference in the systemic
clearance and distribution of GMCSF.
D'Andrea et al. (1998) produced transgenic mice expressing a spontaneous
mutation in the murine Csf2rb1 gene that confers growth
factor-independent proliferation on primary committed myeloid
progenitors. All transgenic mice displayed a myeloproliferative disorder
characterized by splenomegaly, erythrocytosis, and granulocytic and
megakaryocytic hyperplasia. This disorder resembled the human disease
polycythemia vera (263300), suggesting that activating mutations in the
CSF2RB gene may play a role in the pathogenesis of that
myeloproliferative disorder. In addition, the transgenic mice developed
a sporadic, progressive neurologic disorder and displayed bilateral,
symmetrical foci of necrosis in the white matter of the brainstem
associated with an accumulation of macrophages. D'Andrea et al. (1998)
concluded that chronic CSF2RB activation also has the potential to
contribute to pathologic events in the central nervous system.
*FIELD* AV
.0001
SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 5
CSF2RB, 1-BP DEL, 631C
In a Japanese woman with adult-onset pulmonary surfactant metabolism
dysfunction-5 (SMDP5; 614370), manifest as pulmonary alveolar
proteinosis and respiratory insufficiency, Tanaka et al. (2011)
identified a homozygous 1-bp deletion (631delC) in exon 6 of the CSF2RB
gene, resulting in a frameshift and premature termination. Each
unaffected parent was heterozygous for the mutation. GMCSF was very high
in the patient's serum and bronchoalveolar lavage, but autoantibodies to
GMCSF were not found. In vitro studies showed that the patient's
monocytes failed to differentiate into macrophages after stimulation
with GMCSF. There was also a lack of STAT5 (601511) phosphorylation in
response to GMCSF or IL3 stimulation, suggesting defective signaling by
the common beta-subunit of the GMCSF receptor (CSF2RB). Flow cytometry
of patient monocytes showed lack of CSF2RB expression, and CSF2RB mRNA
was not detected in patient cells. Tanaka et al. (2011) speculated that
the late onset in this patient may have been due to compensatory
factors, such as increased serum GMCSF acting through an intact CSF2RA
subunit (306250) or increased levels of other inflammatory cells.
*FIELD* RF
1. D'Andrea, R.; Harrison-Findik, D.; Butcher, C. M.; Finnie, J.;
Blumbergs, P.; Bartley, P.; McCormack, M.; Jones, K.; Rowland, R.;
Gonda, T. J.; Vadas, M. A.: Dysregulated hematopoiesis and a progressive
neurological disorder induced by expression of an activated form of
the human common beta chain in transgenic mice. J. Clin. Invest. 102:
1951-1960, 1998.
2. D'Andrea, R.; Rayner, J.; Moretti, P.; Lopez, A.; Goodall, G. J.;
Gonda, T. J.; Vadas, M.: A mutation of the common receptor subunit
for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating
factor, and IL-5 that leads to ligand independence and tumorigenicity. Blood 83:
2802-2808, 1994.
3. Dirksen, U.; Hattenhorst, U.; Schneider, P.; Schroten, H.; Gobel,
U.; Bocking, A.; Muller, K.-M.; Murray, R.; Burdach, S.: Defective
expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5
receptor common beta chain in children with acute myeloid leukemia
associated with respiratory failure. Blood 92: 1097-1103, 1998.
4. Dirksen, U.; Nishinakamura, R.; Groneck, P.; Hattenhorst, U.; Nogee,
L.; Murray, R.; Burdach, S.: Human pulmonary alveolar proteinosis
associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta
chain expression. J. Clin. Invest. 100: 2211-2217, 1997.
5. Freeburn, R. W.; Gale, R. E.; Wagner, H. M.; Linch, D. C.: The
beta subunit common to the GM-CSF, IL-3 and IL-5 receptors is highly
polymorphic but pathogenic point mutations in patients with acute
myeloid leukaemia (AML) are rare. Leukemia 10: 123-129, 1996.
6. Gorman, D. M.; Itoh, N.; Jenkins, N. A.; Gilbert, D. J.; Copeland,
N. G.; Miyajima, A.: Chromosomal localization and organization of
the murine genes encoding the beta subunits (AIC2A and AIC2B) of the
interleukin 3, granulocyte/macrophage colony-stimulating factor, and
interleukin 5 receptors. J. Biol. Chem. 267: 15842-15848, 1992.
7. Hara, T.; Miyajima, A.: Two distinct functional high affinity
receptors for mouse interleukin-3 (IL-3). EMBO J. 11: 1875-1884,
1992.
8. Hayashida, K.; Kitamura, T.; Gorman, D. M.; Arai, K.; Yokota, T.;
Miyajima, A.: Molecular cloning of a second subunit of the receptor
for human granulocyte-macrophage colony-stimulating factor (GM-CSF):
reconstitution of a high-affinity GM-CSF receptor. Proc. Nat. Acad.
Sci. 87: 9655-9659, 1990.
9. Jenkins, B. J.; D'Andrea, R.; Gonda, T. J.: Activating point mutations
in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors
suggest the involvement of beta subunit dimerization and cell type-specific
molecules in signalling. EMBO J. 14: 4276-4287, 1995.
10. Kao, C.-J.; Chiang, Y.-J.; Chen, P.-H.; Lin, K.-R.; Hwang, P.-I.;
Yang-Yen, H.-F.; Yen, J. J.-Y.: CBAP interacts with the un-liganded
common beta-subunit of the GM-CSF/IL-3/IL-5 receptor and induces apoptosis
via mitochondrial dysfunction. Oncogene 27: 1397-1403, 2008.
11. Kitamura, T.; Sato, N.; Arai, K.; Miyajima, A.: Expression cloning
of the human IL-3 receptor cDNA reveals a shared beta subunit for
the human IL-3 and GM-CSF receptors. Cell 66: 1165-1174, 1991.
12. Kondo, M.; Scherer, D. C.; Miyamoto, T.; King, A. G.; Akashi,
K.; Sugamura, K.; Weissman, I. L.: Cell-fate conversion of lymphoid-committed
progenitors by instructive actions of cytokines. Nature 407: 383-386,
2000.
13. Robb, L.; Drinkwater, C. C.; Metcalf, D.; Li, R.; Kontgen, F.;
Nicola, N. A.; Begley, C. G.: Hematopoietic and lung abnormalities
in mice with a null mutation of the common beta subunit of the receptors
for granulocyte-macrophage colony-stimulating factor and interleukins
3 and 5. Proc. Nat. Acad. Sci. 92: 9565-9569, 1995.
14. Shen, Y.; Baker, E.; Callen, D. F.; Sutherland, G. R.; Willson,
T. A.; Rakar, S.; Gough, N. M.: Localization of the human GM-CSF
receptor beta chain gene (CSF2RB) to chromosome 22q12.2-q13.1. Cytogenet.
Cell Genet. 61: 175-177, 1992.
15. Tanaka, T.; Motoi, N.; Tsuchihashi, Y.; Tazawa, R.; Kaneko, C.;
Nei, T.; Yamamoto, T.; Hayashi, T.; Tagawa, T.; Nagayasu, T.; Kuribayashi,
F.; Ariyoshi, K.; Nakata, K.; Morimoto, K.: Adult-onset hereditary
pulmonary alveolar proteinosis caused by a single-base deletion in
CSF2RB. J. Med. Genet. 48: 205-209, 2011.
16. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/1/2011
Patricia A. Hartz - updated: 4/26/2011
Cassandra L. Kniffin - reorganized: 4/24/2007
Cassandra L. Kniffin - updated: 4/19/2007
Ada Hamosh - updated: 9/20/2000
Victor A. McKusick - updated: 2/3/1999
Victor A. McKusick - updated: 12/21/1998
Victor A. McKusick - updated: 9/29/1998
Victor A. McKusick - updated: 1/20/1998
*FIELD* CD
Victor A. McKusick: 10/4/1991
*FIELD* ED
carol: 09/06/2013
carol: 12/5/2011
ckniffin: 12/1/2011
mgross: 4/26/2011
terry: 6/6/2008
carol: 6/15/2007
carol: 4/24/2007
ckniffin: 4/20/2007
ckniffin: 4/19/2007
alopez: 3/21/2007
terry: 2/26/2007
terry: 2/22/2005
alopez: 9/20/2000
mgross: 2/8/1999
terry: 2/3/1999
carol: 1/29/1999
carol: 12/28/1998
terry: 12/23/1998
terry: 12/21/1998
terry: 10/1/1998
carol: 9/30/1998
terry: 9/29/1998
dkim: 7/23/1998
mark: 1/22/1998
terry: 1/20/1998
terry: 11/6/1995
jason: 6/28/1994
carol: 10/1/1993
carol: 3/1/1993
carol: 12/17/1992
carol: 10/7/1992
*RECORD*
*FIELD* NO
138981
*FIELD* TI
*138981 GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR, BETA; CSF2RB
;;INTERLEUKIN 5 RECEPTOR, BETA; IL5RB;;
read moreINTERLEUKIN 3 RECEPTOR, BETA; IL3RB;;
COMMON BETA CHAIN;;
BETA-C
*FIELD* TX
DESCRIPTION
The CSF2RB gene encodes the high-affinity beta subunit of a receptor for
interleukin-5 (IL5R; 147851), granulocyte-macrophage CSF (CSF2R; 306250)
(Tavernier et al., 1991), and interleukin-3 (IL3RA; 308385) (Kitamura et
al., 1991).
See also the low-affinity alpha subunit of the receptor (CSF2RA; 306250)
CLONING
Hayashida et al. (1990) isolated cDNA clones corresponding to the beta
subunit of the GMCSF receptor from a human erythroleukemia cDNA library.
The deduced 897-amino acid protein had a molecular mass of approximately
120 kD and shares 56% sequence identity with the mouse AIC2B protein.
In the mouse, 2 distinct but related genes, AIC2A (Csf2rb2) and AIC2B
(Csf2rb1), encode the beta subunit common to Csf2r, Il5r, and Il3r
(Gorman et al., 1992). Hara and Miyajima (1992) stated that the mouse
AIC2B gene encodes a common beta subunit for the mouse Gmcsf and Il5
receptors, whereas AIC2A encodes a low-affinity Il3-binding protein by
itself. Hara and Miyajima (1992) found that AIC2A formed a high-affinity
Il3-binding protein when coexpressed with a mouse protein homologous to
the human alpha subunit. In addition, AIC2B formed a high-affinity
Il3-binding protein when coexpressed with the alpha subunit. Thus, the
mouse has 2 high-affinity Il3 receptors, but only the AIC2B gene encodes
a common beta subunit for the mouse Gmcsf, Il5, and Il3 receptors. Robb
et al. (1995) referred to the mouse AIC2B gene as 'beta-c' (for common)
and the AIC2A gene as 'beta-Il3.'
MAPPING
Shen et al. (1992) mapped the human CSF2RB gene to chromosome 22 by PCR
analysis of a series of human/rodent somatic cell hybrids. By
fluorescence in situ hybridization to normal human chromosomes and 2
translocations involving chromosome 22 as well as the chromosome
expressing the rare fragile site FRA22A, they regionalized the gene to
22q12.2-q13.1, proximal to the fragile site.
Gorman et al. (1992) demonstrated that the 2 mouse genes, provisionally
designated Il3rb1 and Il3rb2, are located in the same 250-kb restriction
fragment and map to chromosome 5, closely linked to the Sis locus
(PDGFB; 190040).
GENE FUNCTION
Tavernier et al. (1991) stated that the common receptor subunit, CSF2RB,
that is shared between IL5R and CSF2R provides a molecular basis for the
observation that IL5 (147850) and CSF2 (138960) can partially interfere
with each other's binding and have highly overlapping biologic
activities on eosinophils.
D'Andrea et al. (1994) isolated a mutant form of the IL5RB gene from
growth factor-independent cells that arose spontaneously after infection
of a murine factor-dependent hematopoietic cell line with a retroviral
expression construct of the common beta chain gene. The mutation
consisted of a 37-amino acid duplication of extracellular sequence that
included 2 conserved sequence motifs and conferred ligand-independent
growth on the cells. The results suggested that members of the large
family of cytokine receptors have the capacity to become oncogenically
active.
Jenkins et al. (1995) reported the identification of 2 activating point
mutations in the CSF2RB gene that were generated using a PCR-based
random mutagenesis procedure. By combining this procedure with a
retroviral expression cloning system, they isolated these mutants by
virtue of their ability to confer factor independence on a
factor-dependent hematopoietic cell line. The ability of point mutations
to activate the gene supported the possibility that such mutations could
contribute to human leukemia. In addition, the nature and properties of
these mutants had important implications for the mechanisms of signaling
by the 3 receptors that utilize the common beta subunit. One mutation,
val449-to-glu, was located within the transmembrane domain and, by
analogy with a similar mutation in the NEU oncogene (164870), might act
by inducing dimerization of the common beta subunit. The other mutation,
ile374-to-asn, lay in the extracellular, membrane-proximal portion of
the common beta molecule.
Dirksen et al. (1998) described expression defects of the CSF2RB and/or
the CSF2RA genes in 3 pediatric patients with acute myeloid leukemia
(AML) and pulmonary alveolar proteinosis. Leukemic cells from all 3
patients failed to express express normal levels of beta-c. In addition,
leukemic cells from 2 of the patients lacked expression of CSF2RA, as
shown by flow cytometry. Strikingly reduced or absent function of beta-c
was demonstrated in clonogenic progenitor assays with absent
colony-forming unit growth after GMCSF or IL3 stimulation. The response
to growth factors acting via a growth factor receptor distinct from the
GMCSF/IL3/IL5 system was normal. After antileukemic treatment, the
pulmonary symptoms resolved and beta-c or beta-c plus CSF2RA expression
was normal. Dirksen et al. (1998) concluded that a defect in the CSF2RB
and/or CSF2RA on AML blasts can be associated with respiratory failure
in patients with AML.
Kondo et al. (2000) showed that a clonogenic common lymphoid progenitor,
a bone marrow-resident cell that gives rise exclusively to lymphocytes
(T, B, and natural killer cells), can be redirected to the myeloid
lineage by stimulation through exogenously expressed interleukin-2
receptor (146710) and GMCSF receptor. Analysis of mutants of the beta
chain of the IL2 receptor revealed that the granulocyte and monocyte
differentiation signals are triggered by different cytoplasmic domains,
showing that the signaling pathways responsible for these unique
developmental outcomes are separable. Finally, Kondo et al. (2000)
showed that the endogenous myelomonocytic cytokine receptors for GMCSF
and macrophage colony-stimulating factor (CSF1R; 164770) are expressed
at low to moderate levels on the more primitive hematopoietic stem
cells, are absent on common lymphoid progenitors, and are upregulated
after myeloid lineage induction by IL2 (147680). Kondo et al. (2000)
concluded that cytokine signaling can regulate cell fate decisions and
proposed that a critical step in lymphoid commitment is downregulation
of cytokine receptors that drive myeloid cell development.
Using yeast 2-hybrid, protein pull-down, and coimmunoprecipitation
assays, Kao et al. (2008) showed that CBAP (TMEM102; 613936) interacted
with the box-2 motif of beta-c. Removal of GMCSF increased the amount of
beta-c and CBAP that immunoprecipitated from TF1 erythroleukemia cells
and that colocalized in intracellular compartments. Overexpression of
CBAP in IL3 (147740)-dependent Ba/F3 pro-B cells increased the
percentage of cells showing mitochondrial changes characteristic of
apoptosis and enhanced the apoptotic effect of GMCSF deprivation.
Conversely, knockdown of CBAP in TF1 cells reduced cell sensitivity to
GMCSF deprivation, but not to other proapoptotic stimuli. Kao et al.
(2008) concluded that CBAP binds the isolated beta-c molecule and has a
role in GMCSF deprivation-induced apoptosis.
MOLECULAR GENETICS
Freeburn et al. (1996) failed to find pathogenic mutations in the CSF2RB
gene in 35 patients with acute myeloid leukemia. Although different
patterns were detected in 25 (71%) AML patients and 8 (80%) of 10
healthy controls, all nucleotide changes were found to be polymorphisms.
The authors concluded that the CSF2RB is highly polymorphic, but point
mutations do not appear to contribute to the pathogenesis of AML.
Dirksen et al. (1997) described an expression defect of the CSF2RB gene
in 4 of 7 pediatric patients with pulmonary alveolar proteinosis (see
614370). The patients failed to express normal levels of beta-c, as
shown by flow cytometry. Reduced or absent function of beta-c was
demonstrated by ligand binding studies and progenitor clonogenic assays.
Although molecular analysis of 1 patient identified what the authors
referred to as a pro602-to-thr (P602T) mutation, this change was shown
by Freeburn et al. (1996) to be a polymorphism (P603T with revised
sequence).
In a Japanese woman with adult-onset pulmonary surfactant metabolism
dysfunction-5 (SMDP5; 614370), manifest as pulmonary alveolar
proteinosis, Tanaka et al. (2011) identified a homozygous truncating
mutation in the CSF2RB gene (138981.0001). Each unaffected parent was
heterozygous for the mutation. Tanaka et al. (2011) speculated that the
late onset in this patient may have been due to compensatory factors
such as increased serum GMCSF acting through an intact CSF2RA subunit
(306250) or increased levels of other inflammatory cells.
ANIMAL MODEL
Robb et al. (1995) used gene targeting to create mice with a null
mutation of the common beta subunit of the Csf2rb1 gene (AIC2B). In the
homozygous mice, high-affinity binding of GMCSF (138960) was abolished,
while cells from heterozygous animals showed an intermediate number of
high-affinity receptors. Binding of IL3 (147740) was unaffected,
confirming that the IL3-specific beta-chain remained intact. Homozygous
animals showed reduced eosinophil numbers in peripheral blood and bone
marrow, while other hematologic parameters were normal. In clonal
cultures of homozygous null bone marrow cells, even high concentrations
of GMCSF and IL5 failed to stimulate colony formation, but the cells
exhibited normal quantitative responsiveness to stimulation by IL3 and
other growth factors. The mice exhibited normal development and survived
to young adult life, although they developed pulmonary
peribronchovascular lymphoid infiltrates and areas resembling alveolar
proteinosis. There was no detectable difference in the systemic
clearance and distribution of GMCSF.
D'Andrea et al. (1998) produced transgenic mice expressing a spontaneous
mutation in the murine Csf2rb1 gene that confers growth
factor-independent proliferation on primary committed myeloid
progenitors. All transgenic mice displayed a myeloproliferative disorder
characterized by splenomegaly, erythrocytosis, and granulocytic and
megakaryocytic hyperplasia. This disorder resembled the human disease
polycythemia vera (263300), suggesting that activating mutations in the
CSF2RB gene may play a role in the pathogenesis of that
myeloproliferative disorder. In addition, the transgenic mice developed
a sporadic, progressive neurologic disorder and displayed bilateral,
symmetrical foci of necrosis in the white matter of the brainstem
associated with an accumulation of macrophages. D'Andrea et al. (1998)
concluded that chronic CSF2RB activation also has the potential to
contribute to pathologic events in the central nervous system.
*FIELD* AV
.0001
SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 5
CSF2RB, 1-BP DEL, 631C
In a Japanese woman with adult-onset pulmonary surfactant metabolism
dysfunction-5 (SMDP5; 614370), manifest as pulmonary alveolar
proteinosis and respiratory insufficiency, Tanaka et al. (2011)
identified a homozygous 1-bp deletion (631delC) in exon 6 of the CSF2RB
gene, resulting in a frameshift and premature termination. Each
unaffected parent was heterozygous for the mutation. GMCSF was very high
in the patient's serum and bronchoalveolar lavage, but autoantibodies to
GMCSF were not found. In vitro studies showed that the patient's
monocytes failed to differentiate into macrophages after stimulation
with GMCSF. There was also a lack of STAT5 (601511) phosphorylation in
response to GMCSF or IL3 stimulation, suggesting defective signaling by
the common beta-subunit of the GMCSF receptor (CSF2RB). Flow cytometry
of patient monocytes showed lack of CSF2RB expression, and CSF2RB mRNA
was not detected in patient cells. Tanaka et al. (2011) speculated that
the late onset in this patient may have been due to compensatory
factors, such as increased serum GMCSF acting through an intact CSF2RA
subunit (306250) or increased levels of other inflammatory cells.
*FIELD* RF
1. D'Andrea, R.; Harrison-Findik, D.; Butcher, C. M.; Finnie, J.;
Blumbergs, P.; Bartley, P.; McCormack, M.; Jones, K.; Rowland, R.;
Gonda, T. J.; Vadas, M. A.: Dysregulated hematopoiesis and a progressive
neurological disorder induced by expression of an activated form of
the human common beta chain in transgenic mice. J. Clin. Invest. 102:
1951-1960, 1998.
2. D'Andrea, R.; Rayner, J.; Moretti, P.; Lopez, A.; Goodall, G. J.;
Gonda, T. J.; Vadas, M.: A mutation of the common receptor subunit
for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating
factor, and IL-5 that leads to ligand independence and tumorigenicity. Blood 83:
2802-2808, 1994.
3. Dirksen, U.; Hattenhorst, U.; Schneider, P.; Schroten, H.; Gobel,
U.; Bocking, A.; Muller, K.-M.; Murray, R.; Burdach, S.: Defective
expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5
receptor common beta chain in children with acute myeloid leukemia
associated with respiratory failure. Blood 92: 1097-1103, 1998.
4. Dirksen, U.; Nishinakamura, R.; Groneck, P.; Hattenhorst, U.; Nogee,
L.; Murray, R.; Burdach, S.: Human pulmonary alveolar proteinosis
associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta
chain expression. J. Clin. Invest. 100: 2211-2217, 1997.
5. Freeburn, R. W.; Gale, R. E.; Wagner, H. M.; Linch, D. C.: The
beta subunit common to the GM-CSF, IL-3 and IL-5 receptors is highly
polymorphic but pathogenic point mutations in patients with acute
myeloid leukaemia (AML) are rare. Leukemia 10: 123-129, 1996.
6. Gorman, D. M.; Itoh, N.; Jenkins, N. A.; Gilbert, D. J.; Copeland,
N. G.; Miyajima, A.: Chromosomal localization and organization of
the murine genes encoding the beta subunits (AIC2A and AIC2B) of the
interleukin 3, granulocyte/macrophage colony-stimulating factor, and
interleukin 5 receptors. J. Biol. Chem. 267: 15842-15848, 1992.
7. Hara, T.; Miyajima, A.: Two distinct functional high affinity
receptors for mouse interleukin-3 (IL-3). EMBO J. 11: 1875-1884,
1992.
8. Hayashida, K.; Kitamura, T.; Gorman, D. M.; Arai, K.; Yokota, T.;
Miyajima, A.: Molecular cloning of a second subunit of the receptor
for human granulocyte-macrophage colony-stimulating factor (GM-CSF):
reconstitution of a high-affinity GM-CSF receptor. Proc. Nat. Acad.
Sci. 87: 9655-9659, 1990.
9. Jenkins, B. J.; D'Andrea, R.; Gonda, T. J.: Activating point mutations
in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors
suggest the involvement of beta subunit dimerization and cell type-specific
molecules in signalling. EMBO J. 14: 4276-4287, 1995.
10. Kao, C.-J.; Chiang, Y.-J.; Chen, P.-H.; Lin, K.-R.; Hwang, P.-I.;
Yang-Yen, H.-F.; Yen, J. J.-Y.: CBAP interacts with the un-liganded
common beta-subunit of the GM-CSF/IL-3/IL-5 receptor and induces apoptosis
via mitochondrial dysfunction. Oncogene 27: 1397-1403, 2008.
11. Kitamura, T.; Sato, N.; Arai, K.; Miyajima, A.: Expression cloning
of the human IL-3 receptor cDNA reveals a shared beta subunit for
the human IL-3 and GM-CSF receptors. Cell 66: 1165-1174, 1991.
12. Kondo, M.; Scherer, D. C.; Miyamoto, T.; King, A. G.; Akashi,
K.; Sugamura, K.; Weissman, I. L.: Cell-fate conversion of lymphoid-committed
progenitors by instructive actions of cytokines. Nature 407: 383-386,
2000.
13. Robb, L.; Drinkwater, C. C.; Metcalf, D.; Li, R.; Kontgen, F.;
Nicola, N. A.; Begley, C. G.: Hematopoietic and lung abnormalities
in mice with a null mutation of the common beta subunit of the receptors
for granulocyte-macrophage colony-stimulating factor and interleukins
3 and 5. Proc. Nat. Acad. Sci. 92: 9565-9569, 1995.
14. Shen, Y.; Baker, E.; Callen, D. F.; Sutherland, G. R.; Willson,
T. A.; Rakar, S.; Gough, N. M.: Localization of the human GM-CSF
receptor beta chain gene (CSF2RB) to chromosome 22q12.2-q13.1. Cytogenet.
Cell Genet. 61: 175-177, 1992.
15. Tanaka, T.; Motoi, N.; Tsuchihashi, Y.; Tazawa, R.; Kaneko, C.;
Nei, T.; Yamamoto, T.; Hayashi, T.; Tagawa, T.; Nagayasu, T.; Kuribayashi,
F.; Ariyoshi, K.; Nakata, K.; Morimoto, K.: Adult-onset hereditary
pulmonary alveolar proteinosis caused by a single-base deletion in
CSF2RB. J. Med. Genet. 48: 205-209, 2011.
16. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/1/2011
Patricia A. Hartz - updated: 4/26/2011
Cassandra L. Kniffin - reorganized: 4/24/2007
Cassandra L. Kniffin - updated: 4/19/2007
Ada Hamosh - updated: 9/20/2000
Victor A. McKusick - updated: 2/3/1999
Victor A. McKusick - updated: 12/21/1998
Victor A. McKusick - updated: 9/29/1998
Victor A. McKusick - updated: 1/20/1998
*FIELD* CD
Victor A. McKusick: 10/4/1991
*FIELD* ED
carol: 09/06/2013
carol: 12/5/2011
ckniffin: 12/1/2011
mgross: 4/26/2011
terry: 6/6/2008
carol: 6/15/2007
carol: 4/24/2007
ckniffin: 4/20/2007
ckniffin: 4/19/2007
alopez: 3/21/2007
terry: 2/26/2007
terry: 2/22/2005
alopez: 9/20/2000
mgross: 2/8/1999
terry: 2/3/1999
carol: 1/29/1999
carol: 12/28/1998
terry: 12/23/1998
terry: 12/21/1998
terry: 10/1/1998
carol: 9/30/1998
terry: 9/29/1998
dkim: 7/23/1998
mark: 1/22/1998
terry: 1/20/1998
terry: 11/6/1995
jason: 6/28/1994
carol: 10/1/1993
carol: 3/1/1993
carol: 12/17/1992
carol: 10/7/1992
MIM
614370
*RECORD*
*FIELD* NO
614370
*FIELD* TI
#614370 SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 5; SMDP5
;;PULMONARY ALVEOLAR PROTEINOSIS 5;;
read morePAP DUE TO CSF2RB DEFICIENCY;;
CSF2RB DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because pulmonary surfactant
metabolism dysfunction-5 (SMDP5) can be caused by homozygous mutation in
the CSF2RB gene (138981) on chromosome 22q12.
DESCRIPTION
Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal
recessive lung disorder manifest clinically and pathologically as
pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is a rare
lung disease characterized by the ineffective clearance of surfactant by
alveolar macrophages. This results in the accumulation of
surfactant-derived lipoproteinaceous material in the alveoli and
terminal bronchioles, causing respiratory failure (summary by Greenhill
and Kotton, 2009).
For a general phenotypic description and a discussion of genetic
heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1
(265120).
CLINICAL FEATURES
Dirksen et al. (1997) described an expression defect of the CSF2RB gene
in 4 of 7 pediatric patients with pulmonary alveolar proteinosis. Three
patients were diagnosed as neonates, and 1 at age 1 month, after
presenting with severe respiratory distress. All were
ventilation-dependent. Patient cells failed to express normal levels of
beta-c, as shown by flow cytometry, and reduced or absent function of
beta-c was demonstrated by ligand binding studies and progenitor
clonogenic assays. However, molecular analysis of the CSF2RB gene failed
to identify pathogenic mutations.
Tanaka et al. (2011) reported a Japanese woman, born of consanguineous
parents, who developed gradual dyspnea on exertion beginning at age 36
years. Chest radiographs showed diffuse homogeneous ground-glass
opacities and paving appearance, and lung biopsy showed accumulation of
amorphous eosinophilic material in the alveolar space, consistent with a
diagnosis of pulmonary alveolar proteinosis. GMCSF was very high in
serum and bronchoalveolar lavage, but autoantibodies to GMCSF were not
found. In vitro studies showed that the patient's monocytes failed to
differentiate into macrophages after stimulation with GMCSF. There was
also a lack of STAT5 (601511) phosphorylation in response to GMCSF or
IL3 stimulation, suggesting defective signaling by the common beta
subunit of the GMCSF receptor (CSF2RB). Flow cytometry of patient
monocytes showed lack of CSF2RB expression, and CSF2RB mRNA was not
detected in patient cells. Neither parent was affected.
MOLECULAR GENETICS
In a Japanese woman with late-onset hereditary pulmonary alveolar
proteinosis, Tanaka et al. (2011) identified a homozygous truncating
mutation in the CSF2RB gene (138981.0001). Each unaffected parent was
heterozygous for the mutation. Tanaka et al. (2011) speculated that the
late onset in this patient may have been due to compensatory factors
such as increased serum GMCSF acting through an intact CSF2RA subunit
(306250) or increased levels of other inflammatory cells.
*FIELD* RF
1. Dirksen, U.; Nishinakamura, R.; Groneck, P.; Hattenhorst, U.; Nogee,
L.; Murray, R.; Burdach, S.: Human pulmonary alveolar proteinosis
associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta
chain expression. J. Clin. Invest. 100: 2211-2217, 1997.
2. Greenhill, S. R.; Kotton, D. N.: Pulmonary alveolar proteinosis:
a bench-to-bedside story of granulocyte-macrophage colony-stimulating
factor dysfunction. Chest 136: 571-577, 2009.
3. Tanaka, T.; Motoi, N.; Tsuchihashi, Y.; Tazawa, R.; Kaneko, C.;
Nei, T.; Yamamoto, T.; Hayashi, T.; Tagawa, T.; Nagayasu, T.; Kuribayashi,
F.; Ariyoshi, K.; Nakata, K.; Morimoto, K.: Adult-onset hereditary
pulmonary alveolar proteinosis caused by a single-base deletion in
CSF2RB. J. Med. Genet. 48: 205-209, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
RESPIRATORY:
Respiratory insufficiency;
Dyspnea;
[Lung];
Alveolar proteinosis;
Alveoli filled with granular or foamy surfactant protein exudate;
Granular, hazy, ground-glass interstitial opacifications seen on radiograph
LABORATORY ABNORMALITIES:
Increased serum GM-CSF;
Impaired response to GM-CSF
MISCELLANEOUS:
Onset at age 36 years;
One Japanese woman with a mutation in the CSF2RB gene has been reported
(as of December 2011);
Four unrelated infants with the disorder and decreased expression
of CSF2RB in cells have been reported
MOLECULAR BASIS:
Caused by mutation in the granulocyte-macrophage colony-stimulating
factor receptor, beta (CSF2RB, 138981.0001)
*FIELD* CD
Cassandra L. Kniffin: 12/1/2011
*FIELD* ED
joanna: 12/29/2011
joanna: 12/28/2011
ckniffin: 12/1/2011
*FIELD* CD
Cassandra L. Kniffin: 12/1/2011
*FIELD* ED
carol: 12/05/2011
ckniffin: 12/1/2011
*RECORD*
*FIELD* NO
614370
*FIELD* TI
#614370 SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 5; SMDP5
;;PULMONARY ALVEOLAR PROTEINOSIS 5;;
read morePAP DUE TO CSF2RB DEFICIENCY;;
CSF2RB DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because pulmonary surfactant
metabolism dysfunction-5 (SMDP5) can be caused by homozygous mutation in
the CSF2RB gene (138981) on chromosome 22q12.
DESCRIPTION
Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal
recessive lung disorder manifest clinically and pathologically as
pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is a rare
lung disease characterized by the ineffective clearance of surfactant by
alveolar macrophages. This results in the accumulation of
surfactant-derived lipoproteinaceous material in the alveoli and
terminal bronchioles, causing respiratory failure (summary by Greenhill
and Kotton, 2009).
For a general phenotypic description and a discussion of genetic
heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1
(265120).
CLINICAL FEATURES
Dirksen et al. (1997) described an expression defect of the CSF2RB gene
in 4 of 7 pediatric patients with pulmonary alveolar proteinosis. Three
patients were diagnosed as neonates, and 1 at age 1 month, after
presenting with severe respiratory distress. All were
ventilation-dependent. Patient cells failed to express normal levels of
beta-c, as shown by flow cytometry, and reduced or absent function of
beta-c was demonstrated by ligand binding studies and progenitor
clonogenic assays. However, molecular analysis of the CSF2RB gene failed
to identify pathogenic mutations.
Tanaka et al. (2011) reported a Japanese woman, born of consanguineous
parents, who developed gradual dyspnea on exertion beginning at age 36
years. Chest radiographs showed diffuse homogeneous ground-glass
opacities and paving appearance, and lung biopsy showed accumulation of
amorphous eosinophilic material in the alveolar space, consistent with a
diagnosis of pulmonary alveolar proteinosis. GMCSF was very high in
serum and bronchoalveolar lavage, but autoantibodies to GMCSF were not
found. In vitro studies showed that the patient's monocytes failed to
differentiate into macrophages after stimulation with GMCSF. There was
also a lack of STAT5 (601511) phosphorylation in response to GMCSF or
IL3 stimulation, suggesting defective signaling by the common beta
subunit of the GMCSF receptor (CSF2RB). Flow cytometry of patient
monocytes showed lack of CSF2RB expression, and CSF2RB mRNA was not
detected in patient cells. Neither parent was affected.
MOLECULAR GENETICS
In a Japanese woman with late-onset hereditary pulmonary alveolar
proteinosis, Tanaka et al. (2011) identified a homozygous truncating
mutation in the CSF2RB gene (138981.0001). Each unaffected parent was
heterozygous for the mutation. Tanaka et al. (2011) speculated that the
late onset in this patient may have been due to compensatory factors
such as increased serum GMCSF acting through an intact CSF2RA subunit
(306250) or increased levels of other inflammatory cells.
*FIELD* RF
1. Dirksen, U.; Nishinakamura, R.; Groneck, P.; Hattenhorst, U.; Nogee,
L.; Murray, R.; Burdach, S.: Human pulmonary alveolar proteinosis
associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta
chain expression. J. Clin. Invest. 100: 2211-2217, 1997.
2. Greenhill, S. R.; Kotton, D. N.: Pulmonary alveolar proteinosis:
a bench-to-bedside story of granulocyte-macrophage colony-stimulating
factor dysfunction. Chest 136: 571-577, 2009.
3. Tanaka, T.; Motoi, N.; Tsuchihashi, Y.; Tazawa, R.; Kaneko, C.;
Nei, T.; Yamamoto, T.; Hayashi, T.; Tagawa, T.; Nagayasu, T.; Kuribayashi,
F.; Ariyoshi, K.; Nakata, K.; Morimoto, K.: Adult-onset hereditary
pulmonary alveolar proteinosis caused by a single-base deletion in
CSF2RB. J. Med. Genet. 48: 205-209, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
RESPIRATORY:
Respiratory insufficiency;
Dyspnea;
[Lung];
Alveolar proteinosis;
Alveoli filled with granular or foamy surfactant protein exudate;
Granular, hazy, ground-glass interstitial opacifications seen on radiograph
LABORATORY ABNORMALITIES:
Increased serum GM-CSF;
Impaired response to GM-CSF
MISCELLANEOUS:
Onset at age 36 years;
One Japanese woman with a mutation in the CSF2RB gene has been reported
(as of December 2011);
Four unrelated infants with the disorder and decreased expression
of CSF2RB in cells have been reported
MOLECULAR BASIS:
Caused by mutation in the granulocyte-macrophage colony-stimulating
factor receptor, beta (CSF2RB, 138981.0001)
*FIELD* CD
Cassandra L. Kniffin: 12/1/2011
*FIELD* ED
joanna: 12/29/2011
joanna: 12/28/2011
ckniffin: 12/1/2011
*FIELD* CD
Cassandra L. Kniffin: 12/1/2011
*FIELD* ED
carol: 12/05/2011
ckniffin: 12/1/2011