ID IL2RA_HUMAN Reviewed; 272 AA. AC P01589; Q5W007; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 01-MAY-2013, entry version 148. DE RecName: Full=Interleukin-2 receptor subunit alpha; DE Short=IL-2 receptor subunit alpha; DE Short=IL-2-RA; DE Short=IL-2R subunit alpha; DE Short=IL2-RA; DE AltName: Full=TAC antigen; DE AltName: Full=p55; DE AltName: CD_antigen=CD25; DE Flags: Precursor; GN Name=IL2RA; 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]. RX PubMed=6090949; DOI=10.1038/311631a0; RA Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., RA Uchiyama T., Yodoi J., Honjo T.; RT "Molecular cloning of cDNA encoding human interleukin-2 receptor."; RL Nature 311:631-635(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6090948; DOI=10.1038/311626a0; RA Leonard W.J., Depper J.M., Crabtree G.R., Rudikoff S., Pumphrey J., RA Robb R.J., Kroenke M., Svetlik P.B., Peffer N.J., Waldmann T.A., RA Greene W.C.; RT "Molecular cloning and expression of cDNAs for the human interleukin-2 RT receptor."; RL Nature 311:626-631(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2999698; DOI=10.1093/nar/13.21.7579; RA Ishida N., Kanamori H., Noma T., Nikaido T., Sabe H., Suzuki N., RA Shimizu A., Honjo T.; RT "Molecular cloning and structure of the human interleukin 2 receptor RT gene."; RL Nucleic Acids Res. 13:7579-7589(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2996141; DOI=10.1126/science.2996141; RA Leonard W.J., Depper J.M., Kanehisa M., Kroenke M., Peffer N.J., RA Svetlik P.B., Sullivan M., Greene W.C.; RT "Structure of the human interleukin-2 receptor gene."; RL Science 230:633-639(1985). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-272. RG SeattleSNPs variation discovery resource; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21. RX PubMed=3030566; DOI=10.1016/0092-8674(87)90754-9; RA Cross S.L., Feinberg M.B., Wolf J.B., Holbrook N.J., Wong-Stall F., RA Leonard W.J.; RT "Regulation of the human interleukin-2 receptor alpha chain promoter: RT activation of a nonfunctional promoter by the transactivator gene of RT HTLV-I."; RL Cell 49:47-56(1987). RN [9] RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-70; ASN-89; THR-218; RP THR-224; THR-229 AND THR-237. RX PubMed=3134887; DOI=10.1016/0006-291X(88)90695-X; RA Miedel M.C., Hulmes J.D., Weber D.V., Bailon P., Pan Y.C.; RT "Structural analysis of recombinant soluble human interleukin-2 RT receptor. Primary structure, assignment of disulfide bonds and core RT IL-2 binding structure."; RL Biochem. Biophys. Res. Commun. 154:372-379(1988). RN [10] RP 3D-STRUCTURE MODELING OF 23-83. RX PubMed=7529123; DOI=10.1016/S0969-2126(94)00085-9; RA Bamborough P., Hedgecock C.J., Richards W.G.; RT "The interleukin-2 and interleukin-4 receptors studied by molecular RT modelling."; RL Structure 2:839-851(1994). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 22-238 IN COMPLEX WITH IL2; RP IL2RB AND IL2RC, AND DISULFIDE BONDS. RX PubMed=16293754; DOI=10.1126/science.1117893; RA Wang X., Rickert M., Garcia K.C.; RT "Structure of the quaternary complex of interleukin-2 with its alpha, RT beta, and gammac receptors."; RL Science 310:1159-1163(2005). RN [12] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 22-233 IN COMPLEX WITH IL2; RP IL2RB AND IL2RC, AND DISULFIDE BONDS. RX PubMed=16477002; DOI=10.1073/pnas.0511161103; RA Stauber D.J., Debler E.W., Horton P.A., Smith K.A., Wilson I.A.; RT "Crystal structure of the IL-2 signaling complex: paradigm for a RT heterotrimeric cytokine receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 103:2788-2793(2006). RN [13] RP INVOLVEMENT IN IDDM10. RX PubMed=17676041; DOI=10.1038/ng2102; RA Lowe C.E., Cooper J.D., Brusko T., Walker N.M., Smyth D.J., Bailey R., RA Bourget K., Plagnol V., Field S., Atkinson M., Clayton D.G., RA Wicker L.S., Todd J.A.; RT "Large-scale genetic fine mapping and genotype-phenotype associations RT implicate polymorphism in the IL2RA region in type 1 diabetes."; RL Nat. Genet. 39:1074-1082(2007). CC -!- FUNCTION: Receptor for interleukin-2. CC -!- SUBUNIT: Non-covalent dimer of an alpha and a beta subunit. IL2R CC exists in 3 different forms: a high affinity dimer, an CC intermediate affinity monomer (beta subunit), and a low affinity CC monomer (alpha subunit). The high and intermediate affinity forms CC also associate with a gamma subunit. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- DISEASE: Diabetes mellitus, insulin-dependent, 10 (IDDM10) CC [MIM:601942]: A multifactorial disorder of glucose homeostasis CC that is characterized by susceptibility to ketoacidosis in the CC absence of insulin therapy. Clinical fetaures are polydipsia, CC polyphagia and polyuria which result from hyperglycemia-induced CC osmotic diuresis and secondary thirst. These derangements result CC in long-term complications that affect the eyes, kidneys, nerves, CC and blood vessels. Note=Disease susceptibility is associated with CC variations affecting the gene represented in this entry. CC -!- SIMILARITY: Contains 2 Sushi (CCP/SCR) domains. CC -!- WEB RESOURCE: Name=IL2RAbase; Note=IL2RA mutation db; CC URL="http://bioinf.uta.fi/IL2RAbase/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/il2ra/"; 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; X01057; CAA25525.1; -; mRNA. DR EMBL; X03131; CAA26906.1; -; Genomic_DNA. DR EMBL; X03132; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03133; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03134; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03135; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03136; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03137; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; X03138; CAA26906.1; JOINED; Genomic_DNA. DR EMBL; K03122; AAB59535.1; ALT_SEQ; mRNA. DR EMBL; M11066; AAA67527.1; -; Genomic_DNA. DR EMBL; M10322; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11060; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11061; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11062; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11063; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11064; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; M11065; AAA67527.1; JOINED; Genomic_DNA. DR EMBL; AY563103; AAS55572.1; -; Genomic_DNA. DR EMBL; AL157395; CAH73595.1; -; Genomic_DNA. DR EMBL; AL137186; CAH73595.1; JOINED; Genomic_DNA. DR EMBL; AL137186; CAI41069.1; -; Genomic_DNA. DR EMBL; AL157395; CAI41069.1; JOINED; Genomic_DNA. DR EMBL; CH471072; EAW86414.1; -; Genomic_DNA. DR EMBL; M15864; AAA59162.1; -; Genomic_DNA. DR EMBL; BN000945; CAK26553.1; -; Genomic_DNA. DR IPI; IPI00003101; -. DR PIR; A44186; UHHU2. DR RefSeq; NP_000408.1; NM_000417.2. DR UniGene; Hs.231367; -. DR PDB; 1ILM; Model; -; A=23-83. DR PDB; 1ILN; Model; -; A=23-83. DR PDB; 1Z92; X-ray; 2.80 A; B=22-238. DR PDB; 2B5I; X-ray; 2.30 A; D=22-238. DR PDB; 2ERJ; X-ray; 3.00 A; A/E=22-233. DR PDB; 3IU3; X-ray; 2.90 A; I/J/K=22-238. DR PDB; 3NFP; X-ray; 2.86 A; I/K=22-238. DR PDBsum; 1ILM; -. DR PDBsum; 1ILN; -. DR PDBsum; 1Z92; -. DR PDBsum; 2B5I; -. DR PDBsum; 2ERJ; -. DR PDBsum; 3IU3; -. DR PDBsum; 3NFP; -. DR ProteinModelPortal; P01589; -. DR DIP; DIP-1080N; -. DR STRING; 9606.ENSP00000369293; -. DR PhosphoSite; P01589; -. DR DMDM; 124317; -. DR PaxDb; P01589; -. DR PRIDE; P01589; -. DR DNASU; 3559; -. DR Ensembl; ENST00000379959; ENSP00000369293; ENSG00000134460. DR GeneID; 3559; -. DR KEGG; hsa:3559; -. DR UCSC; uc001iiz.2; human. DR CTD; 3559; -. DR GeneCards; GC10M006041; -. DR HGNC; HGNC:6008; IL2RA. DR HPA; CAB002419; -. DR MIM; 147730; gene. DR MIM; 601942; phenotype. DR MIM; 606367; phenotype. DR neXtProt; NX_P01589; -. DR Orphanet; 169100; Immunodeficiency due to CD25 deficiency. DR PharmGKB; PA29828; -. DR eggNOG; NOG47154; -. DR HOGENOM; HOG000113044; -. DR HOVERGEN; HBG052109; -. DR InParanoid; P01589; -. DR KO; K05068; -. DR OMA; QAELCDD; -. DR OrthoDB; EOG4C2HB5; -. DR PhylomeDB; P01589; -. DR Pathway_Interaction_DB; arf6_traffickingpathway; Arf6 trafficking events. DR Pathway_Interaction_DB; nfat_tfpathway; Calcineurin-regulated NFAT-dependent transcription in lymphocytes. DR Pathway_Interaction_DB; tcrcalciumpathway; Calcium signaling in the CD4+ TCR pathway. DR Pathway_Interaction_DB; cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells. DR Pathway_Interaction_DB; il12_stat4pathway; IL12 signaling mediated by STAT4. DR Pathway_Interaction_DB; il12_2pathway; IL12-mediated signaling events. DR Pathway_Interaction_DB; il2_pi3kpathway; IL2 signaling events mediated by PI3K. DR Pathway_Interaction_DB; il2_stat5pathway; IL2 signaling events mediated by STAT5. DR Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events. DR Reactome; REACT_6900; Immune System. DR BindingDB; P01589; -. DR ChEMBL; CHEMBL1778; -. DR DrugBank; DB00041; Aldesleukin. DR DrugBank; DB00074; Basiliximab. DR DrugBank; DB00111; Daclizumab. DR DrugBank; DB00004; Denileukin diftitox. DR EvolutionaryTrace; P01589; -. DR GenomeRNAi; 3559; -. DR NextBio; 13900; -. DR ArrayExpress; P01589; -. DR Bgee; P01589; -. DR CleanEx; HS_IL2RA; -. DR Genevestigator; P01589; -. DR GermOnline; ENSG00000134460; Homo sapiens. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Compara. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008144; F:drug binding; IEA:Compara. DR GO; GO:0004911; F:interleukin-2 receptor activity; TAS:ProtInc. DR GO; GO:0006924; P:activation-induced cell death of T cells; IEA:Compara. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEA:Compara. DR GO; GO:0050687; P:negative regulation of defense response to virus; IEA:Compara. DR GO; GO:0050777; P:negative regulation of immune response; IEA:Compara. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Compara. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Compara. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Compara. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Compara. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Compara. DR GO; GO:0045582; P:positive regulation of T cell differentiation; IEA:Compara. DR GO; GO:0046013; P:regulation of T cell homeostatic proliferation; IEA:Compara. DR InterPro; IPR015486; IL-2_recpt_a. DR InterPro; IPR000436; Sushi_SCR_CCP. DR PANTHER; PTHR10573; PTHR10573; 1. DR Pfam; PF00084; Sushi; 2. DR SMART; SM00032; CCP; 2. DR SUPFAM; SSF57535; Complement_control_module; 2. DR PROSITE; PS50923; SUSHI; 2. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Diabetes mellitus; Disulfide bond; KW Glycoprotein; Membrane; Polymorphism; Receptor; Reference proteome; KW Repeat; Signal; Sushi; Transmembrane; Transmembrane helix. FT SIGNAL 1 21 FT CHAIN 22 272 Interleukin-2 receptor subunit alpha. FT /FTId=PRO_0000011024. FT TOPO_DOM 22 240 Extracellular (Potential). FT TRANSMEM 241 259 Helical; (Potential). FT TOPO_DOM 260 272 Cytoplasmic (Potential). FT DOMAIN 22 84 Sushi 1. FT DOMAIN 123 186 Sushi 2. FT CARBOHYD 70 70 N-linked (GlcNAc...). FT CARBOHYD 89 89 N-linked (GlcNAc...). FT CARBOHYD 218 218 O-linked (GalNAc...). FT CARBOHYD 224 224 O-linked (GalNAc...). FT CARBOHYD 229 229 O-linked (GalNAc...). FT CARBOHYD 237 237 O-linked (GalNAc...). FT DISULFID 24 168 FT DISULFID 49 80 FT DISULFID 51 82 FT DISULFID 67 125 FT DISULFID 152 184 FT VARIANT 272 272 I -> T (in dbSNP:rs12722712). FT /FTId=VAR_019280. FT STRAND 34 37 FT STRAND 39 41 FT STRAND 46 48 FT STRAND 55 57 FT STRAND 63 67 FT STRAND 74 77 FT STRAND 82 84 FT STRAND 135 137 FT STRAND 143 145 FT STRAND 147 152 FT STRAND 157 162 FT STRAND 164 170 FT STRAND 172 174 FT STRAND 175 177 FT STRAND 182 185 SQ SEQUENCE 272 AA; 30819 MW; 83D907C8C81D2C0E CRC64; MDSYLLMWGL LTFIMVPGCQ AELCDDDPPE IPHATFKAMA YKEGTMLNCE CKRGFRRIKS GSLYMLCTGN SSHSSWDNQC QCTSSATRNT TKQVTPQPEE QKERKTTEMQ SPMQPVDQAS LPGHCREPPP WENEATERIY HFVVGQMVYY QCVQGYRALH RGPAESVCKM THGKTRWTQP QLICTGEMET SQFPGEEKPQ ASPEGRPESE TSCLVTTTDF QIQTEMAATM ETSIFTTEYQ VAVAGCVFLL ISVLLLSGLT WQRRQRKSRR TI //