Interleukin-23 receptor

The interleukin-23 receptor is a type I cytokine receptor. It is encoded in human by the IL23R gene.[5] In complex with the interleukin-12 receptor β1 subunit (IL-12Rβ1), it is activated by the cytokine interleukin 23 (IL-23).[6] 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, an N-terminal fibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains.[6] There are 24 IL23R splice variants in mitogen-activated lymphocytes.[7] IL23R includes some single-nucleotide polymorphisms in the region encoding the domain that binds IL-23, which may lead to differences between people in Th17 activation.[8] 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.[9]

IL23R
Identifiers
AliasesIL23R, interleukin 23 receptor
External IDsOMIM: 607562 MGI: 2181693 HomoloGene: 16930 GeneCards: IL23R
Orthologs
SpeciesHumanMouse
Entrez

149233

209590

Ensembl

ENSG00000162594

ENSMUSG00000049093

UniProt

Q5VWK5

Q8K4B4

RefSeq (mRNA)

NM_144701

NM_144548

RefSeq (protein)

NP_653302

NP_653131

Location (UCSC)Chr 1: 67.14 – 67.26 MbChr 6: 67.4 – 67.47 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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) and also binds to transcription activator STAT3 in a ligand-dependent manner.[5]

Clinical significance

Three variants in the IL23R gene have been shown to protect against Crohn's disease and ulcerative colitis.[10][11][12] The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.[13]

Model organisms

A conditional knockout mouse line called Il23rtm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[14] Male and female animals underwent a standardized phenotypic screen[15] to determine the effects of deletion.[16][17][18][19] In-depth immunological phenotyping was also undertaken.[20]

References
  1. GRCh38: Ensembl release 89: ENSG00000162594 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000049093 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: IL23R interleukin 23 receptor".
  6. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. (June 2002). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". Journal of Immunology. 168 (11): 5699–708. doi:10.4049/jimmunol.168.11.5699. PMID 12023369.
  7. Kan SH, Mancini G, Gallagher G (October 2008). "Identification and characterization of multiple splice forms of the human interleukin-23 receptor alpha chain in mitogen-activated leukocytes". Genes and Immunity. 9 (7): 631–9. doi:10.1038/gene.2008.64. PMID 18754016.
  8. Yu RY, Brazaitis J, Gallagher G (February 2015). "The human IL-23 receptor rs11209026 A allele promotes the expression of a soluble IL-23R-encoding mRNA species". Journal of Immunology. 194 (3): 1062–8. doi:10.4049/jimmunol.1401850. PMID 25552541.
  9. "Figure 8. with two source data miR-34a regulates Th17 cell-mediated proliferation". doi:10.7554/elife.39479.025. {{cite journal}}: Cite journal requires |journal= (help)
  10. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science. 314 (5804): 1461–3. Bibcode:2006Sci...314.1461D. doi:10.1126/science.1135245. PMC 4410764. PMID 17068223.
  11. Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. (Nov 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nature Genetics. 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.
  12. Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, et al. (Jan 2011). "Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease". Nature Genetics. 43 (1): 43–7. doi:10.1038/ng.733. hdl:1854/LU-1145381. PMID 21151126. S2CID 21340871.
  13. de Paus RA, van de Wetering D, van Dissel JT, van de Vosse E (September 2008). "IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants". Molecular Immunology. 45 (15): 3889–95. doi:10.1016/j.molimm.2008.06.029. PMID 18675459.
  14. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  15. "International Mouse Phenotyping Consortium".
  16. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  19. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  20. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading
  • Overview of all the structural information available in the PDB for UniProt: Q5VWK5 (Interleukin-23 receptor) at the PDBe-KB.
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