The interleukin-23 receptor is a
type I cytokine receptor
Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name '' hemopoietin receptors'', and share a ...
. It is encoded in human by the ''IL23R'' gene.
In complex with the interleukin-12 receptor β1 subunit (
IL-12Rβ1), it is activated by the cytokine
interleukin 23
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit (which is shared with IL-12) and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 (t ...
(IL-23).
The ''IL23R'' mRNA is 2.8 kilobases in length and includes 12 exons. The translated protein contains 629 amino acids; it is a type I penetrating protein and includes a
signal peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16–30 amino acids long) present at the ...
, an
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
fibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains.
There are 24 ''IL23R'' splice variants in mitogen-activated lymphocytes. ''IL23R'' includes some
single-nucleotide polymorphisms
In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...
in the region encoding the domain that binds IL-23, which may lead to differences between people in
Th17
T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. Howe ...
activation. There is also a variant of IL-23R that consists of just the extracellular part and is known as soluble IL-23R. This form can compete with the membrane-bound form to bind IL-23, modulating the Th17 immune response and regulation of inflammation and immune function.
Function
The protein encoded by this gene is a subunit of the receptor for
IL-23. This protein pairs with the receptor molecule IL-12Rβ1 (
IL12RB1), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 (
JAK2
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF ...
) and also binds to transcription activator
STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family.
Function
STAT3 is a member of the STAT protein family. In respon ...
in a ligand-dependent manner.
Clinical significance
Three variants in the ''IL23R'' gene have been shown to protect against
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
and
ulcerative colitis
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
.
The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.
References
Further reading
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External links
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{{Interleukin receptor modulators
Type I cytokine receptors