IL2RA

Protein identityUniProt · HPA

UniProt accession

P01589

Gene

IL2RA

Ensembl

ENSG00000134460

Chromosome

10

Canonical length

272 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins

OverviewNCBI Gene

The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolyisis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is presently unknown. Mutations in this gene are associated with interleukin 2 receptor alpha deficiency. Patients with severe Coronavirus Disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have significantly elevated levels of IL2R in their plasma. Similarly, serum IL-2R levels are found to be elevated in patients with different types of carcinomas. Certain IL2RA and IL2RB gene polymorphisms have been associated with lung cancer risk. [provided by RefSeq, Jul 2020]

Canonical amino-acid sequenceUniProt

272 residues, UniProt reviewed canonical sequence.

>P01589|IL2RA
     1  MDSYLLMWGL LTFIMVPGCQ AELCDDDPPE IPHATFKAMA YKEGTMLNCE CKRGFRRIKS
    61  GSLYMLCTGN SSHSSWDNQC QCTSSATRNT TKQVTPQPEE QKERKTTEMQ SPMQPVDQAS
   121  LPGHCREPPP WENEATERIY HFVVGQMVYY QCVQGYRALH RGPAESVCKM THGKTRWTQP
   181  QLICTGEMET SQFPGEEKPQ ASPEGRPESE TSCLVTTTDF QIQTEMAATM ETSIFTTEYQ
   241  VAVAGCVFLL ISVLLLSGLT WQRRQRKSRR TI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL2RA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.48

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL2RA.

Disease | AllUniProt

Conditions IL2RA is implicated in, by any mechanism.

• Type 1 diabetes mellitus 10 (T1D10) MIM:601942
• Immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) MIM:606367

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 383 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency due to CD25 deficiency
• Type 1 diabetes mellitus 10

Disease | AutoantibodyPubMed

Conditions in which antibodies against IL2RA are reported. Each links to that disease's full target list.

• Thyroiditis, Autoimmune 8
• Encephalomyelitis, Autoimmune, Experimental 5
• Diabetes Mellitus, Type 1 4
• Graves Disease 3

Showing 4 of 5 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for IL2RA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.66

gnomAD pLI

0.05

gnomAD missense Z

0.36

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activated T cell proliferation
• activation-induced cell death of T cells
• apoptotic process
• cell surface receptor signaling pathway
• immune response
• inflammatory response
• inflammatory response to antigenic stimulus
• interleukin-2-mediated signaling pathway
• negative regulation of inflammatory response
• negative regulation of T cell proliferation
• Notch signaling pathway
• positive regulation of activated T cell proliferation
• positive regulation of T cell differentiation
• regulation of CD4-positive, alpha-beta T cell proliferation
• regulation of T cell homeostatic proliferation
• regulation of T cell tolerance induction

Molecular functions

• interleukin-2 binding
• interleukin-2 receptor activity

Cellular components

• external side of plasma membrane
• interleukin-2 receptor complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Sushi/SCR/CCP superfamily
• Sushi repeat (SCR repeat)
• Interleukin-2 receptor alpha

KeywordsUniProt

• Diabetes mellitus
• Disulfide bond
• Glycoprotein
• Immunity
• Membrane
• Receptor
• Repeat
• Signal
• Sushi
• Transmembrane
• Transmembrane helix