Quaternary Structure: Complexes

Interleukin-2 receptor

Interleukin-15 receptor

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	551	22q12.3	IL2RB	interleukin 2 receptor subunit beta
Mouse	1	539	15 37.52 cM	Il2rb	interleukin 2 receptor, beta chain
Rat	1	537	7q34	Il2rb	interleukin 2 receptor subunit beta

Previous and Unofficial Names

CD122 | IL15RB | interleukin 15 receptor, beta | high affinity IL-2 receptor subunit beta | IL-2R subunit beta | IL-15 receptor beta chain | IL-2/15Rbeta | interleukin 2 receptor

Database Links
Alphafold	P14784 (Hs), P16297 (Mm), P26896 (Rn)
CATH/Gene3D	2.60.40.10
ChEMBL Target	CHEMBL3276 (Hs)
DrugBank Target	P14784 (Hs)
Ensembl Gene	ENSG00000100385 (Hs), ENSMUSG00000068227 (Mm), ENSRNOG00000048636 (Rn)
Entrez Gene	3560 (Hs), 16185 (Mm), 25746 (Rn)
Human Protein Atlas	ENSG00000100385 (Hs)
KEGG Gene	hsa:3560 (Hs), mmu:16185 (Mm), rno:25746 (Rn)
OMIM	146710 (Hs)
Pharos	P14784 (Hs)
UniProtKB	P14784 (Hs), P16297 (Mm), P26896 (Rn)
Wikipedia	IL2RB (Hs)

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Agonists
Key to terms and symbols		Click column headers to sort
Ligand Sp. Action Value Parameter Reference bempegaldesleukin Hs Agonist 5.8 pKd 1 ⤷ pKd 5.8 (Kd 1.769x10-6 M) [1] Description: Binding affinity of 1-PEG-IL2 for IL2Rβ determined using surface plasmon resonance (SPR), measured on a Biacore® instrument.

Immunopharmacology Comments

IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R.

Immuno Process Associations

Immuno Process:  Cytokine production & signalling

Immuno Process:  Inflammation

Immuno Process:  Cellular signalling

Biologically Significant Variants
Type:  Missense mutation Species:  Human Description:  A homozygous missense mutation that decreases IL2Rβ response to IL-2, likely due to disruption of the receptor/ligand interaction site. This mutant allele was identified in a kindred of Saudi Arabian origin. Amino acid change:  Ser40Leu References:  3
Type:  Truncation Species:  Human Description:  A mutation that introduces a premature stop codon which severly truncates the IL2Rβ protein and results in complete loss of expression of functional receptor, and subsequently no IL-2 signalling. This mutant allele was identified in a kindred of Romany origin. It is associated with a severe phenotype including failure of fetal development, perinatal death and fetal loss in utero. Amino acid change:  Gln96STOP References:  3
Type:  Missense mutation Species:  Human Description:  A homozygous missense mutation that causes nascent IL2Rβ protein to be sequestered in the endoplasmic reticulum and results in loss of receptor expression at the cell membrane. This mutant allele was identified in two separate kindreds of Pakistani and south Asian origin. Phenotypically the homozygotes with this variant exhibit reduced T cell function, but retain some NK cell-responsiveness to IL-2. Amino acid change:  Leu77Pro References:  3
Type:  In-frame deletion Species:  Human Description:  A homozygous 9-nucleotide in-frame deletion that results in the loss of three amino acids in the highly conserved WSXWS extracellular motif of IL2Rβ. The WSXWS motif affects receptor protein folding, trafficking, binding and signalling. The homozygous individuals have reduced expression of functional IL2Rβ and dysregulated IL-2/15 signalling. This causes a severe primary immune deficiency that is characterised by reduced circulating Treg cells and a higher than normal frequency of immature NK cells. This mutation was identified in two infant siblings of consanguineous parents from Tajikistan. Amino acid change:  Pro222_Gln225del References:  2
Biologically Significant Variant Comments
Mutations in the human IL2RB gene have been identified as causing life-threatening immune dysregulation in a number of patients. In two independent studies (both published in the same 2019 issue of the Journal of Experimental Medicine), several loss-of-function mutations were discovered in patients suffering from primary immune deficiency, and which were characterised by a similar constellation of clinical manifestations (including bowel inflammation, dermatological abnormalities, lymphadenopathy, cytomegalovirus viremia, hypergammaglobulinemia and autoantibody production) [2-3].