P01589 (IL2RA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-2 receptor subunit alpha
Short name=IL-2 receptor subunit alpha
Short name=IL-2-RA
Short name=IL-2R subunit alpha
Short name=IL2-RA

Alternative name(s):
TAC antigen
p55
CD_antigen=CD25

Gene names

Name:

IL2RA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	272 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for interleukin-2.
Subunit structure	Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Diabetes mellitus, insulin-dependent, 10 (IDDM10) [MIM:601942]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.13
Sequence similarities	Contains 2 Sushi (CCP/SCR) domains.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus
Domain	Repeat Signal Sushi Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from electronic annotation. Source: Compara activation-induced cell death of T cells Inferred from electronic annotation. Source: Compara apoptotic process Traceable author statement PubMed 9096364. Source: ProtInc cell proliferation Traceable author statement PubMed 2983318. Source: ProtInc immune response Traceable author statement PubMed 9096364. Source: ProtInc inflammatory response to antigenic stimulus Inferred from electronic annotation. Source: Compara negative regulation of T cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of defense response to virus Inferred from electronic annotation. Source: Compara negative regulation of immune response Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of activated T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara regulation of T cell homeostatic proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	drug binding Inferred from electronic annotation. Source: Compara interleukin-2 receptor activity Traceable author statement PubMed 9096364. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 272

251

Interleukin-2 receptor subunit alpha

PRO_0000011024

Regions

Topological domain

22 – 240

219

Extracellular Potential

Transmembrane

241 – 259

19

Helical; Potential

Topological domain

260 – 272

13

Cytoplasmic Potential

Domain

22 – 84

63

Sushi 1

Domain

123 – 186

64

Sushi 2

Amino acid modifications

Glycosylation

70

1

N-linked (GlcNAc...) Ref.9

Glycosylation

89

1

N-linked (GlcNAc...) Ref.9

Glycosylation

218

1

O-linked (GalNAc...) Ref.9

Glycosylation

224

1

O-linked (GalNAc...) Ref.9

Glycosylation

229

1

O-linked (GalNAc...) Ref.9

Glycosylation

237

1

O-linked (GalNAc...) Ref.9

Disulfide bond

24 ↔ 168

Ref.9 Ref.11 Ref.12

Disulfide bond

49 ↔ 80

Ref.9 Ref.11 Ref.12

Disulfide bond

51 ↔ 82

Ref.9 Ref.11 Ref.12

Disulfide bond

67 ↔ 125

Ref.9 Ref.11 Ref.12

Disulfide bond

152 ↔ 184

Ref.9 Ref.11 Ref.12

Natural variations

Natural variant

272

1

I → T. Ref.5
Corresponds to variant rs12722712 [ dbSNP | Ensembl ].

VAR_019280

Secondary structure

1

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272

Helix Strand Turn

Details...

Beta strand

34 – 37

4

Beta strand

39 – 41

3

Beta strand

46 – 48

3

Beta strand

55 – 57

3

Beta strand

63 – 67

5

Beta strand

74 – 77

4

Beta strand

82 – 84

3

Beta strand

135 – 137

3

Beta strand

143 – 145

3

Beta strand

147 – 152

6

Beta strand

157 – 162

6

Beta strand

164 – 170

7

Beta strand

172 – 174

3

Beta strand

175 – 177

3

Beta strand

182 – 185

4

Sequences

	Sequence		Length	Mass (Da)
	P01589 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 83D907C8C81D2C0E	FASTA	272	30,819
	10 20 30 40 50 60 MDSYLLMWGL LTFIMVPGCQ AELCDDDPPE IPHATFKAMA YKEGTMLNCE CKRGFRRIKS 70 80 90 100 110 120 GSLYMLCTGN SSHSSWDNQC QCTSSATRNT TKQVTPQPEE QKERKTTEMQ SPMQPVDQAS 130 140 150 160 170 180 LPGHCREPPP WENEATERIY HFVVGQMVYY QCVQGYRALH RGPAESVCKM THGKTRWTQP 190 200 210 220 230 240 QLICTGEMET SQFPGEEKPQ ASPEGRPESE TSCLVTTTDF QIQTEMAATM ETSIFTTEYQ 250 260 270 VAVAGCVFLL ISVLLLSGLT WQRRQRKSRR TI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of cDNA encoding human interleukin-2 receptor." Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Nature 311:631-635(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and expression of cDNAs for the human interleukin-2 receptor." Leonard W.J., Depper J.M., Crabtree G.R., Rudikoff S., Pumphrey J., Robb R.J., Kroenke M., Svetlik P.B., Peffer N.J., Waldmann T.A., Greene W.C. Nature 311:626-631(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular cloning and structure of the human interleukin 2 receptor gene." Ishida N., Kanamori H., Noma T., Nikaido T., Sabe H., Suzuki N., Shimizu A., Honjo T. Nucleic Acids Res. 13:7579-7589(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structure of the human interleukin-2 receptor gene." Leonard W.J., Depper J.M., Kanehisa M., Kroenke M., Peffer N.J., Svetlik P.B., Sullivan M., Greene W.C. Science 230:633-639(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	SeattleSNPs variation discovery resource Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-272.
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I." Cross S.L., Feinberg M.B., Wolf J.B., Holbrook N.J., Wong-Stall F., Leonard W.J. Cell 49:47-56(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
[9]	"Structural analysis of recombinant soluble human interleukin-2 receptor. Primary structure, assignment of disulfide bonds and core IL-2 binding structure." Miedel M.C., Hulmes J.D., Weber D.V., Bailon P., Pan Y.C. Biochem. Biophys. Res. Commun. 154:372-379(1988) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-70; ASN-89; THR-218; THR-224; THR-229 AND THR-237.
[10]	"The interleukin-2 and interleukin-4 receptors studied by molecular modelling." Bamborough P., Hedgecock C.J., Richards W.G. Structure 2:839-851(1994) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 23-83.
[11]	"Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors." Wang X., Rickert M., Garcia K.C. Science 310:1159-1163(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 22-238 IN COMPLEX WITH IL2; IL2RB AND IL2RC, DISULFIDE BONDS.
[12]	"Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor." Stauber D.J., Debler E.W., Horton P.A., Smith K.A., Wilson I.A. Proc. Natl. Acad. Sci. U.S.A. 103:2788-2793(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 22-233 IN COMPLEX WITH IL2; IL2RB AND IL2RC, DISULFIDE BONDS.
[13]	"Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes." Lowe C.E., Cooper J.D., Brusko T., Walker N.M., Smyth D.J., Bailey R., Bourget K., Plagnol V., Field S., Atkinson M., Clayton D.G., Wicker L.S., Todd J.A. Nat. Genet. 39:1074-1082(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN IDDM10.
+	Additional computationally mapped references.

Web resources

IL2RAbase

IL2RA mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X01057 mRNA. Translation: CAA25525.1.
X03131 , X03132, X03133, X03134, X03135, X03136, X03137, X03138 Genomic DNA. Translation: CAA26906.1.
K03122 mRNA. Translation: AAB59535.1. Sequence problems.
M11066 , M10322, M11060, M11061, M11062, M11063, M11064, M11065 Genomic DNA. Translation: AAA67527.1.
AY563103 Genomic DNA. Translation: AAS55572.1.
AL157395, AL137186 Genomic DNA. Translation: CAH73595.1.
AL137186, AL157395 Genomic DNA. Translation: CAI41069.1.
CH471072 Genomic DNA. Translation: EAW86414.1.
M15864 Genomic DNA. Translation: AAA59162.1.
BN000945 Genomic DNA. Translation: CAK26553.1.

IPI

IPI00003101.

PIR

UHHU2. A44186.

RefSeq

NP_000408.1. NM_000417.2.

UniGene

Hs.231367.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ILM	model	-	A	23-83	[»]
1ILN	model	-	A	23-83	[»]
1Z92	X-ray	2.80	B	22-238	[»]
2B5I	X-ray	2.30	D	22-238	[»]
2ERJ	X-ray	3.00	A/E	22-233	[»]
3IU3	X-ray	2.90	I/J/K	22-238	[»]
3NFP	X-ray	2.86	I/K	22-238	[»]

ProteinModelPortal

P01589.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1080N.

MINT

MINT-8146732.

STRING

9606.ENSP00000369293.

PTM databases

PhosphoSite

P01589.

Polymorphism databases

DMDM

124317.

Proteomic databases

PaxDb

P01589.

PRIDE

P01589.

Protocols and materials databases

DNASU

3559.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379959; ENSP00000369293; ENSG00000134460.

GeneID

3559.

KEGG

hsa:3559.

UCSC

uc001iiz.2. human.

Organism-specific databases

CTD

3559.

GeneCards

GC10M006041.

HGNC

HGNC:6008. IL2RA.

HPA

CAB002419.

MIM

147730. gene.
601942. phenotype.
606367. phenotype.

neXtProt

NX_P01589.

Orphanet

169100. Immunodeficiency due to CD25 deficiency.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.

PharmGKB

PA29828.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47154.

HOGENOM

HOG000113044.

HOVERGEN

HBG052109.

InParanoid

P01589.

KO

K05068.

OMA

QAELCDD.

OrthoDB

EOG4C2HB5.

PhylomeDB

P01589.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.
nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01589.

Bgee

P01589.

CleanEx

HS_IL2RA.

Genevestigator

P01589.

GermOnline

ENSG00000134460. Homo sapiens.

Family and domain databases

InterPro

IPR015486. IL-2_recpt_a.
IPR000436. Sushi_SCR_CCP.
[Graphical view]

PANTHER

PTHR10573. PTHR10573. 1 hit.

Pfam

PF00084. Sushi. 2 hits.
[Graphical view]

SMART

SM00032. CCP. 2 hits.
[Graphical view]

SUPFAM

SSF57535. Complement_control_module. 2 hits.

PROSITE

PS50923. SUSHI. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P01589.

ChEMBL

CHEMBL1778.

DrugBank

DB00041. Aldesleukin.
DB00074. Basiliximab.
DB00111. Daclizumab.
DB00004. Denileukin diftitox.

EvolutionaryTrace

P01589.

GenomeRNAi

3559.

NextBio

13900.

SOURCE

Search...

Entry information

Entry name

IL2RA_HUMAN

Accession

Primary (citable) accession number: P01589
Secondary accession number(s): Q5W007

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.