I27RA_HUMAN
ID I27RA_HUMAN Reviewed; 636 AA.
AC Q6UWB1; A0N0L1; O60624;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Interleukin-27 receptor subunit alpha;
DE Short=IL-27 receptor subunit alpha;
DE Short=IL-27R subunit alpha;
DE Short=IL-27R-alpha;
DE Short=IL-27RA;
DE AltName: Full=Cytokine receptor WSX-1;
DE AltName: Full=Cytokine receptor-like 1;
DE AltName: Full=Type I T-cell cytokine receptor;
DE Short=TCCR;
DE AltName: Full=ZcytoR1;
DE Flags: Precursor;
GN Name=IL27RA; Synonyms=CRL1, TCCR, WSX1; ORFNames=UNQ296/PRO336;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Erythroleukemia;
RX PubMed=9600072; DOI=10.1006/bbrc.1998.8576;
RA Sprecher C.A., Grant F.J., Baumgartner J.W., Presnell S.R., Schrader S.K.,
RA Yamagiwa T., Whitmore T.E., O'Hara P.J., Foster D.F.;
RT "Cloning and characterization of a novel class I cytokine receptor.";
RL Biochem. Biophys. Res. Commun. 246:82-90(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang W., Wan T., He L., Yuan Z., Cao X.;
RT "A novel gp130-like cytokine receptor.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=11057672; DOI=10.1038/35038103;
RA Chen Q., Ghilardi N., Wang H., Baker T., Xie M.-H., Gurney A., Grewal I.S.,
RA de Sauvage F.J.;
RT "Development of Th1-type immune responses requires the type I cytokine
RT receptor TCCR.";
RL Nature 407:916-920(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTIONAL COMPLEX WITH IL6ST.
RX PubMed=14764690; DOI=10.4049/jimmunol.172.4.2225;
RA Pflanz S., Hibbert L., Mattson J., Rosales R., Vaisberg E., Bazan J.F.,
RA Phillips J.H., McClanahan T.K., de Waal Malefyt R., Kastelein R.A.;
RT "WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for
RT IL-27.";
RL J. Immunol. 172:2225-2231(2004).
RN [8]
RP FUNCTION, AND IDENTIFICATION IN HUMANIN RECEPTOR COMPLEX.
RX PubMed=19386761; DOI=10.1091/mbc.e09-02-0168;
RA Hashimoto Y., Kurita M., Aiso S., Nishimoto I., Matsuoka M.;
RT "Humanin inhibits neuronal cell death by interacting with a cytokine
RT receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130.";
RL Mol. Biol. Cell 20:2864-2873(2009).
CC -!- FUNCTION: Receptor for IL27. Requires IL6ST/GP130 to mediate signal
CC transduction in response to IL27. This signaling system acts through
CC STAT3 and STAT1. Acts as a receptor for the neuroprotective peptide
CC humanin as part of a complex with IL6ST/GP130 and CNTFR
CC (PubMed:19386761). Involved in the regulation of Th1-type immune
CC responses. Also appears to be involved in innate defense mechanisms.
CC {ECO:0000269|PubMed:14764690, ECO:0000269|PubMed:19386761}.
CC -!- SUBUNIT: Component of a receptor complex composed of IL6ST/GP130,
CC IL27RA/WSX1 and CNTFR which interacts with the neuroprotective peptide
CC humanin. {ECO:0000269|PubMed:19386761}.
CC -!- INTERACTION:
CC Q6UWB1; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-19045531, EBI-12244618;
CC Q6UWB1; P57739: CLDN2; NbExp=3; IntAct=EBI-19045531, EBI-751440;
CC Q6UWB1; Q5J5C9: DEFB121; NbExp=3; IntAct=EBI-19045531, EBI-10244198;
CC Q6UWB1; Q96Q80: DERL3; NbExp=3; IntAct=EBI-19045531, EBI-12831318;
CC Q6UWB1; Q8N3T1: GALNT15; NbExp=3; IntAct=EBI-19045531, EBI-3925203;
CC Q6UWB1; Q6N075: MFSD5; NbExp=3; IntAct=EBI-19045531, EBI-3920969;
CC Q6UWB1; Q96JW4: SLC41A2; NbExp=3; IntAct=EBI-19045531, EBI-10290130;
CC Q6UWB1; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-19045531, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in lymphoid tissues such as
CC spleen, lymph nodes and peripheral blood leukocytes. Weakly expressed
CC in other tissues examined including heart, brain, fetal and adult lung,
CC liver, skeletal muscle, kidney, pancreas, prostate, testis, ovary,
CC small intestine, kidney and colon. In the lymphoid system, higher level
CC expression in CD4+ T-cell subsets than in CD8+ T-cell subsets. Also
CC weaker expression in CD19+ B-cells and monocytes.
CC {ECO:0000269|PubMed:11057672, ECO:0000269|PubMed:9600072}.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; AF053004; AAC39755.1; -; mRNA.
DR EMBL; AF106912; AAG26090.1; -; mRNA.
DR EMBL; AF265242; AAG27297.1; -; mRNA.
DR EMBL; EF064719; ABK41902.1; -; Genomic_DNA.
DR EMBL; AY358876; AAQ89235.1; -; mRNA.
DR EMBL; BC028003; AAH28003.1; -; mRNA.
DR CCDS; CCDS12303.1; -.
DR PIR; JW0047; JW0047.
DR RefSeq; NP_004834.1; NM_004843.3.
DR AlphaFoldDB; Q6UWB1; -.
DR BioGRID; 114852; 75.
DR IntAct; Q6UWB1; 36.
DR STRING; 9606.ENSP00000263379; -.
DR GlyGen; Q6UWB1; 7 sites.
DR iPTMnet; Q6UWB1; -.
DR PhosphoSitePlus; Q6UWB1; -.
DR BioMuta; IL27RA; -.
DR DMDM; 116242518; -.
DR EPD; Q6UWB1; -.
DR jPOST; Q6UWB1; -.
DR MassIVE; Q6UWB1; -.
DR MaxQB; Q6UWB1; -.
DR PaxDb; Q6UWB1; -.
DR PeptideAtlas; Q6UWB1; -.
DR PRIDE; Q6UWB1; -.
DR ProteomicsDB; 67462; -.
DR Antibodypedia; 13590; 483 antibodies from 35 providers.
DR DNASU; 9466; -.
DR Ensembl; ENST00000263379.4; ENSP00000263379.1; ENSG00000104998.4.
DR Ensembl; ENST00000672064.1; ENSP00000500946.1; ENSG00000288185.1.
DR GeneID; 9466; -.
DR KEGG; hsa:9466; -.
DR MANE-Select; ENST00000263379.4; ENSP00000263379.1; NM_004843.4; NP_004834.1.
DR UCSC; uc002mxx.5; human.
DR CTD; 9466; -.
DR DisGeNET; 9466; -.
DR GeneCards; IL27RA; -.
DR HGNC; HGNC:17290; IL27RA.
DR HPA; ENSG00000104998; Tissue enhanced (lymphoid).
DR MIM; 605350; gene.
DR neXtProt; NX_Q6UWB1; -.
DR OpenTargets; ENSG00000104998; -.
DR PharmGKB; PA134891276; -.
DR VEuPathDB; HostDB:ENSG00000104998; -.
DR eggNOG; ENOG502RF72; Eukaryota.
DR GeneTree; ENSGT00700000104610; -.
DR HOGENOM; CLU_029896_0_0_1; -.
DR InParanoid; Q6UWB1; -.
DR OMA; TCCCSLI; -.
DR OrthoDB; 204535at2759; -.
DR PhylomeDB; Q6UWB1; -.
DR TreeFam; TF338122; -.
DR PathwayCommons; Q6UWB1; -.
DR Reactome; R-HSA-8984722; Interleukin-35 Signalling.
DR Reactome; R-HSA-9020956; Interleukin-27 signaling.
DR SignaLink; Q6UWB1; -.
DR SIGNOR; Q6UWB1; -.
DR BioGRID-ORCS; 9466; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; IL27RA; human.
DR GeneWiki; Interleukin_27_receptor,_alpha_subunit; -.
DR GenomeRNAi; 9466; -.
DR Pharos; Q6UWB1; Tbio.
DR PRO; PR:Q6UWB1; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6UWB1; protein.
DR Bgee; ENSG00000104998; Expressed in granulocyte and 96 other tissues.
DR Genevisible; Q6UWB1; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0042022; C:interleukin-12 receptor complex; IBA:GO_Central.
DR GO; GO:0072536; C:interleukin-23 receptor complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0045509; F:interleukin-27 receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:2000408; P:negative regulation of T cell extravasation; IEA:Ensembl.
DR GO; GO:2000317; P:negative regulation of T-helper 17 type immune response; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0002829; P:negative regulation of type 2 immune response; IEA:Ensembl.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IBA:GO_Central.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IEA:Ensembl.
DR GO; GO:0048302; P:regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 3.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 3.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..636
FT /note="Interleukin-27 receptor subunit alpha"
FT /id="PRO_0000010876"
FT TOPO_DOM 33..516
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 517..537
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 538..636
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 131..231
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 322..417
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 419..511
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 587..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 217..221
FT /note="WSXWS motif"
FT MOTIF 554..562
FT /note="Box 1 motif"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 467
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 7
FT /note="A -> G (in Ref. 3; AAG27297 and 5; AAQ89235)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 636 AA; 69474 MW; DC7DAAABA643CE97 CRC64;
MRGGRGAPFW LWPLPKLALL PLLWVLFQRT RPQGSAGPLQ CYGVGPLGDL NCSWEPLGDL
GAPSELHLQS QKYRSNKTQT VAVAAGRSWV AIPREQLTMS DKLLVWGTKA GQPLWPPVFV
NLETQMKPNA PRLGPDVDFS EDDPLEATVH WAPPTWPSHK VLICQFHYRR CQEAAWTLLE
PELKTIPLTP VEIQDLELAT GYKVYGRCRM EKEEDLWGEW SPILSFQTPP SAPKDVWVSG
NLCGTPGGEE PLLLWKAPGP CVQVSYKVWF WVGGRELSPE GITCCCSLIP SGAEWARVSA
VNATSWEPLT NLSLVCLDSA SAPRSVAVSS IAGSTELLVT WQPGPGEPLE HVVDWARDGD
PLEKLNWVRL PPGNLSALLP GNFTVGVPYR ITVTAVSASG LASASSVWGF REELAPLVGP
TLWRLQDAPP GTPAIAWGEV PRHQLRGHLT HYTLCAQSGT SPSVCMNVSG NTQSVTLPDL
PWGPCELWVT ASTIAGQGPP GPILRLHLPD NTLRWKVLPG ILFLWGLFLL GCGLSLATSG
RCYHLRHKVL PRWVWEKVPD PANSSSGQPH MEQVPEAQPL GDLPILEVEE MEPPPVMESS
QPAQATAPLD SGYEKHFLPT PEELGLLGPP RPQVLA
